deslorelin and histrelin

Topics: Adolescent; Body Mass Index; Child; Epilepsy; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Obesity; Ovary; Puberty, Precocious; Testis; Triptorelin Pamoate

Topics: Adult; Age Determination by Skeleton; Age Factors; Body Height; Buserelin; Child; Clinical Trials as Topic; Female; Gonadotropin-Releasing Hormone; Humans; Male; Nafarelin; Prognosis; Puberty, Precocious; Triptorelin Pamoate

Concern has been raised that children with central precocious puberty (CPP) are prone to the development of obesity. Here we report longitudinal height, weight, and body mass index (BMI) data from 96 girls and 14 boys with CPP before, during, and after GnRH agonist (GnRHa) administration. Skinfold thickness (n = 46) and percent body fat by dual energy x-ray absorptiometry (n = 21) were determined in subsets for more accurate assessment of body composition and to validate the use of the BMI SD score as an index of body fatness in our subjects. Before the initiation of therapy (PRE), the girls with CPP had a mean BMI SD score for chronological age (CA) of 1.1+/-0.1 and for bone age (BA) of 0.1+/-0.1. By the end of the study, 12-24 months after the discontinuation of GnRHa, the mean BMI SD score was 0.9+/-0.1 for CA and 0.6+/-0.1 for BA. At the visit when GnRHa was discontinued, 41% and 22% of the girls had a BMI SD score for CA more than the 85th and 95th percentiles, respectively, indicating that obesity was present at a high rate among our subjects; the BMI SD score for CA at the PRE visit was its strongest predictor. Indeed, 86% of the girls with BMI SD score for CA above the 85th percentile when GnRHa was discontinued also had BMI SD score for CA above the 85th percentile at the PRE visit. The proportion of boys with elevated BMI SD score for CA was also high. Fifty-four percent and 31% of the SD scores were greater than the 85th and 95th percentiles after 36 months of GnRHa therapy; the BMI SD score for CA PRE had been above the 85th percentile in 71% of these overweight subjects. Obesity occurs at a high rate among children with CPP, but does not appear to be related to long term pituitary-gonadal suppression induced by GnRHa administration. Children with CPP should have a baseline BMI SD score calculated, and those at risk for obesity should be counseled appropriately.

Topics: Adolescent; Body Composition; Body Height; Body Mass Index; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Male; Obesity; Puberty, Precocious; Skinfold Thickness; Triptorelin Pamoate; Weight Gain

In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure.

Topics: Age Determination by Skeleton; Body Height; Child; Child, Preschool; Estrogens; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Plate; Humans; Puberty; Puberty, Precocious; Regression Analysis; Time Factors; Triptorelin Pamoate

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3 +/- 2.1 yr old at the start of treatment and were treated with either deslorelin (4 microg/kg.d sc) or histrelin (4-10 microg/kg.d) for an average of 6.1 +/- 2.5 yr. Final height averaged 159.8 +/- 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 +/- 9.6 cm) but still significantly less than midparental height (MPH) (163.7 +/- 5.6). Final height averaged 171.1 +/- 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 +/- 14.2 cm) but still significantly less than MPH (178.3 +/- 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height SD score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

Topics: Age Factors; Body Height; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Infant; Male; Puberty, Precocious; Triptorelin Pamoate

Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 microg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4-8 microg/kg x day, s.c.) or histrelin (10 microg/kg x day, s.c.) for 3.1-10.3 yr and were observed at 1, 2, 3, and 4-5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that whereas the peak LH level was higher in HH than in IPP girls before (165.5 +/- 129 vs. 97.5 +/- 55.7; P < 0.02) and at the end (6.8 +/- 6.0 vs. 3.9 +/- 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH levels in both HH and IPP groups tended to be lower than normal, whereas the peak FSH levels were not different from normal, so that the overall posttherapy LH/FSH ratio was decreased compared to that in the normal girls (HH, 2.7 +/- 0.3; IPP, 2.6 +/- 0.1; normal, 5.2 +/- 4.8; P < 0.05). The MOV was larger in HH than IPP at the end of treatment (3.7 +/- 3.5 vs. 2.0 +/- 1.2 mL; P < 0.05) and tended to increase in both groups over time to become larger than that in normal girls by 4-5 yr posttherapy (HH, 14.9 +/- 12.9; IPP, 7.6 +/- 2.2; normal, 5.4 +/- 2.5 mL; P < 0.05). Whereas the onset of spontaneous menses varied widely in both groups, once menses had started, the HH group had a higher incidence of oligomenorrhea. Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular menses. Live births of normal infants were reported by 2 HH and 2 IPP patients, and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients. BMI was greater than normal in HH

Topics: Adolescent; Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Luteinizing Hormone; Pregnancy; Puberty, Precocious; Reproduction; Triptorelin Pamoate