To evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). Seventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. HV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( =2.78 and 2.20, all < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( >0.05), and both were higher than that in no intervention group (162±4 cm, < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. Long term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.
Adolescent ; Body Height ; Bone Development ; Child ; Gonadotropin-Releasing Hormone ; Growth Disorders ; Humans ; Letrozole ; therapeutic use ; Male

PURPOSE: Obesity is a well-known risk factor for central precocious puberty (CPP). Recently, elevated thyroid stimulating hormone (TSH) was reported in obese youth. However, few data regarding the relationship between CPP and TSH are available. The aim of this study was to evaluate thyroid function in girls with CPP and the relationship between CPP and serum TSH concentration. METHODS: This was a retrospective cross-sectional study. A total of 1,247 girls aged between 6.0 and 8.9 years who had undergone a gonadotropin-releasing hormone (GnRH) stimulation test to determine the presence of puberty were studied. Subjects were classified into CPP (n=554) and non-CPP (n=693) groups according to the results of the GnRH stimulation test. Characteristics and laboratory data of the CPP and non-CPP groups were compared and correlations between those characteristics and laboratory data and TSH concentration were evaluated. Serum TSH concentration in the CPP group was higher than that of the non-CPP group (3.19±1.55 mIU/L vs. 2.58±1.34 mIU/L, P<0.001). RESULTS: Serum free thyroxine (fT4) concentration in the CPP group was notably lower than that of the non-CPP group (1.38±0.14 ng/dL vs. 1.44±0.18 ng/dL, P<0.001). Across all subjects, 149 girls (11.9%) had hyperthyrotropinemia. The prevalence of hyperthyrotropinemia was higher in the CPP group compared to the non-CPP group (15.7% vs. 8.9%, P<0.001). TSH concentrations were positively correlated with age, height, weight, BMI, bone age, bone age advance, insulin-like growth factor 1 (IGF-1), IGF-1 standard deviation score, basal luteinizing hormone (LH), peak LH and basal follicle-stimulation hormone. TSH concentrations were negatively correlated with fT4. Multiple linear regression analysis showed that age (β=0.548, P<0.001) and peak LH (β=0.019, P=0.008) were independently associated with serum TSH concentration. CONCLUSIONS: Hyperthyrotropinemia in girls with CPP tends to be associated with pubertal LH elevation. In conclusion, pubertal onset may be associated with thyroid function.
Adolescent ; Cross-Sectional Studies ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Insulin-Like Growth Factor I ; Linear Models ; Luteinizing Hormone ; Obesity ; Prevalence ; Puberty ; Puberty, Precocious ; Retrospective Studies ; Risk Factors ; Thyroid Gland ; Thyrotropin ; Thyroxine

PURPOSE: This study aimed to investigate the outcomes of gonadotropin-releasing hormone agonist (GnRHa) therapy with or without growth hormone (GH) therapy for girls with idiopathic central precocious puberty (CPP). METHODS: The medical records of 166 girls diagnosed with CPP from 2002 to 2017 were retrospectively reviewed. All included patients were treated with GnRHa for ≥36 months. Changes in height standard deviation score (SDS) for bone age, chronological age (CA), and predicted adult height (PAH) were assessed for the first three years of treatment. The final height gain SDS was calculated as the difference between the initial PAH SDS and adult height (AH) SDS; these were then compared between the GnRHa group (group A, n=135) and the combined GnRHa/GH group (group B, n=31).
Adolescent ; Adult ; Body Height ; Female ; Gonadotropin-Releasing Hormone ; Growth Hormone ; Humans ; Medical Records ; Puberty ; Puberty, Precocious ; Retrospective Studies

PURPOSE: Predicted adult height (PAH) is often crucial to decision-making about treatment with human growth hormone (GH) or gonadotropin-releasing hormone agonist in children with short stature. This study compares final adult height (FAH) with different methods used to determine PAH and assesses the clinical utility and analytical validity of height prediction for children not treated with GH. METHODS: Clinical findings were retrospectively analyzed, and the heights of 44 children (22 males and 22 females) who visited our clinic between August 2006 and June 2017 and reached near final adult height (NFAH) were evaluated. Children treated with GH were excluded. We compared measured NFAH to PAH using the Bayley-Pinneau (BP), Tanner-Whitehouse Mark 2, and Roche-Wainer-Thissen (RWT) methods. RESULTS: Pearson correlation between all 3 prediction methods and NFAH showed high positive correlations in males and females (P < 0.05). The average difference between PAH and NFAH for the BP method (0.4±3.9 cm) was significantly lower than those for the RWT and TW 2 methods in females (P=0.000, analysis of variance). Furthermore, only PAH by the BP method in females was very close to measured NFAH (paired t-test). A Bland-Altman plot verified that 95% of the differences between the PAH and NFAH exist between limits of agreement (mean±1.96 standard deviation). CONCLUSIONS: The BP method is more useful to predict NFAH in females than other methods. Careful attention is still required when using such tools because PAH can be inaccurate. Therefore, a more accurate FAH prediction model for Korean children is needed.
Adult ; Child* ; Female ; Gonadotropin-Releasing Hormone ; Human Growth Hormone ; Humans ; Male ; Methods* ; Retrospective Studies

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2–8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.
Animals ; Cricetinae* ; Cricetulus ; Cyclophosphamide ; Fertility ; Gonadotropins ; Growth Hormone-Releasing Hormone ; Humans ; In Situ Nick-End Labeling ; Infertility ; Infertility, Male* ; Male ; Male* ; Pregnancy Rate ; Reproduction ; Testis ; Testosterone ; Vacuoles

PURPOSE: Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO). MATERIALS AND METHODS: We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015. RESULTS: The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL. CONCLUSION: Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.
Aromatase Inhibitors* ; Aromatase* ; Breast Neoplasms* ; Breast* ; Cohort Studies ; Disease-Free Survival ; Female ; Gonadotropin-Releasing Hormone* ; Humans ; Multivariate Analysis ; Ovariectomy ; Phenobarbital ; Premenopause ; Propensity Score ; Receptor, Epidermal Growth Factor ; Retrospective Studies

OBJECTIVETo develop a new method for predicting adult height (PAH) based on the theory of Bayley-Pinneau and to evaluate the feasibility of this method in predicting adult height of girls with idiopathic central precocious puberty (ICPP) who were treated with gonadotropin releasing hormone agonist (GnRHa).

METHOD(1) The new method for PAH, i.e. PAH = Height/percentage of adult height for bone age, was established according to the theory of Bayley-Pinneau and the data from the national growth survey of children in the nine cities of China in the year 2005. (2) Data from seventeen female patients with ICPP received GnRHa treatment and achieved final adult height (FAH) were collected. Before and during the treatment, PAH was calculated by the method of Bayley-Pinneau and the new method.

RESULTThe mean FAH(cm) of the 17 patients with ICPP was 159.81 ± 4.95. The PAH (cm), before and after treatment for 1, 2 and 3 years, were 156.53 ± 3.63, 157.71 ± 3.62, 158.60 ± 3.50, 161.46 ± 4.50 and 161.56 ± 3.77, 161.68 ± 3.44, 162.04 ± 4.42, 163.13 ± 2.36 respectively by using the new method (PAH-D) and Bayley-Pinneau method(PAH-BP). The mean value of (PAH-D-FAH) and (PAH-BP-FAH) were -1.96 cm and 1.48 cm. However, the 95% confidence interval was (-3.82 cm to -0.11 cm), (-1.60 cm to 4.55 cm) for (PAH-D-FAH) and (PAH-BP -FAH). There was no significant difference between the values obtained before and after treatment in terms of PAH by use of Bayley-Pinneau method. By the new method, however, the results showed that the PAH increased and improved further with prolonged treatment periods. And at the end of treatment, there was no significant difference between PAH and FAH. The correlation coefficient was 0.93. Regression analysis showed that the trend line was in parallel with baseline data.

CONCLUSIONThe new method we established could predict better the final heights of girls with CPP who were treated with GnRHa.

Adult ; Body Height ; Child ; China ; Drug Therapy, Combination ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Human Growth Hormone ; Humans ; Puberty, Precocious ; drug therapy ; Reference Values

OBJECTIVETo determine the effect of gonadotropin releasing hormone agonist (GnRHa), by itself alone or in combination with recombinant human growth hormone (rhGH), on height in young girls (bone age≥10 years) with idiopathic central precocious puberty (ICPP).

METHODSEighty girls with ICPP (9.0±0.7 years old) from six medical centers across Southeast and Southwest China participated in this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18 ±0.53 years) were treated with GnRHa for 25.29±6.92 months and rhGH for 12.87±7.02 months. Girls in the GnRHa group (bone age 11.03 ±0.50 years) were treated with GnRHa for 25.96±8.95 months. The height standard deviation for bone age (HtSDS-BA), predicted adult height, near-adult height and net height increase before and after treatment were recorded for girls in both groups.

RESULTSHtSDS-BA was significantly improved after treatment for both groups (P<0.01) and the HtSDS-BA value was superior in the GnRHa+rhGH group over the GnRHa group (P<0.01). Values in near adult height (157±6 cm vs 157±4 cm), net height increase after treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal (161±5 cm vs 158±5 cm) were higher in the GnRHa+rhGH group than the GnRHa group, but the differences were not significant.

CONCLUSIONSBoth GnRHa plus rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a bone age ≥10 years to a similar extent. Adult height predicted based on bone age in ICPP girls following drug withdrawal is usually overestimated and precautions should be taken when this parameter is used.

Body Height ; drug effects ; Child ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; pharmacology ; Human Growth Hormone ; pharmacology ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology

OBJECTIVETo observe the effect of electro-acupuncture (EA) on clinical outcomes and the occurrence of ovarian hyperstimulation syndrome (OHSS) in in vitro fertilization and embryo transplantation.

METHODSTotally 109 patients who routinely received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Reproductive Center were assigned to the control group (56 cases) and the EA group (53 cases) according to even and odd-numbered date. Patients in the control group received controlled ovarian hyperstimulation (COH) referring to GnRH-a long protocol. On the basis of COH, those in the EA group received EA from the day of Gn injection to the day of embryo transfer. Estradiol (E2), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and angiotensin (AT) II were measured in all patients on the day of hCG injection, the day of ovum pick up (OPU), and the day of embryo transfer (ET), respectively. The oocyte retrieval rate, good quality embryo rate, clinical pregnancy rate, the abortion rate, and the occurrence of OHSS were compared between the two groups.

RESULTSCompared with the control group, serum E2 levels on the day of OPU and the day of ET were significantly lower in the EA group (P < 0.05). On the day of OPU levels of VEGF and IL-6 also significantly decreased (P < 0.05). Serum levels of VEGF and IL-6 reached the highest line on the day of hCG in the two groups, and then showed a decreasing trend. Compared with the control group at the same time point, serum levels of VEGF and IL-6 obviously decreased on on the day of OPU, hCG, and ET (P < 0.05). The occurrence of OHSS and the canceling rate of transplant cycle were significantly lower in the EA group than in the control group (P < 0.05).

CONCLUSIONSEA, as an adjunctive therapy, could reduce the occurrence of OHSS in IVF. Besides, it did not decrease good embryo rates and pregnancy rates in IVF-ET, which might be associated with lowering local vascular permeability of ovaries.

Electroacupuncture ; methods ; Embryo Transfer ; Estradiol ; metabolism ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; metabolism ; Humans ; Interleukin-6 ; metabolism ; Ovarian Hyperstimulation Syndrome ; therapy ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Sperm Injections, Intracytoplasmic ; Vascular Endothelial Growth Factor A ; metabolism

PURPOSE: There is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa) in central precocious puberty (CPP). We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH) in girls with CPP. METHODS: We reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS) for bone age (BA), and compared adult height (AH) with midparental height (MPH) and predicted adult height (PAH) during treatment in groups received GnRHa alone (n=59) or GnRHa plus GH (n=23). RESULTS: In the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4+/-4.23 cm) was significantly higher than the initial PAH (156.6+/-3.96 cm) (P<0.001), and it was similar to the MPH (159.9+/-3.52 cm). In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3+/-5.33 cm) was also higher than the initial PAH (154.6+/-2.55 cm) (P<0.001), which was similar to the MPH (158.1+/-3.31 cm). Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment. CONCLUSION: In CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.
Adult* ; Female ; Gonadotropin-Releasing Hormone* ; Growth Hormone* ; Humans ; Medical Records ; Puberty, Precocious* ; Treatment Outcome