Gonadotropin-releasing Hormone Analog Treatment Research Articles

Combination of gonadotropin-releasing hormone (GnRH) agonists with GnRH antagonists before chemotherapy reduce but does not completely prevent a follicle-stimulating hormone flare-up

Increasing evidence supports GnRH agonists to be an effective treatment to preserve ovarian function during chemotherapy, but the initial flare-up of FSH during the first week after GnRH agonist application still limits its use. The combination of GnRH agonists with GnRH antagonists might solve this problem to some extent as the addition of GnRH antagonists at least significantly reduces the FSH flare-up.

An enhanced leiomyoma cell response to osmotic stress is central to the mechanism of gonadotropin releasing hormone analogue treatment

OBJECTIVE: Clinical treatment of leiomyomas with gonadotropin releasing hormone (GnRH) analogue produces a rapid reduction in leiomyoma volume, but rapid regrowth occurs when treatment is withdrawn, suggesting a central role for osmotic regulation. We have previously demonstrated that transcription factor, Nuclear Factor of Activated T cells 5 (NFAT5) is augmented in human leiomyomas under osmotic stress. In these studies, we determined the role of GnRH analogue treatment in leiomyoma cell osmotic regulation.

Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

Background. Loss of bone density with androgen deprivation therapy for prostate cancer is well recognized. We assessed the effects of quarterly infusion of zoledronic acid on bone mineral density (BMD) and markers of bone turnover over a one-year period in men receiving gonadotropin-releasing hormone analog (GnRH-a) for prostate cancer. Methods. 41 subjects were randomly assigned to treatment with zoledronic acid (4 mg) IV infusion or placebo every 3 months. The primary endpoint was the change in the lumbar spine BMD after 12 months of treatment. Results. The change in vertebral BMD in the zoledronic acid group (+7.93 ± 1.4%) was significantly (P < .05) greater than the change in the placebo group (+0.82 ± 1.7%) as was the change in left femoral neck BMD (+5.05 ± 1.4% for the zoledronic acid group versus −0.48 ± 1.4% for the placebo group). The decrease in biochemical markers of bone turnover was significantly (P < .05) greater in the zoledronic acid group compared to the placebo group. Conclusion. Quarterly infusion of zoledronic acid for 1 year improved vertebral and left femoral neck BMD with a decrease in bone turnover markers in men on GnRH-a treatment. Zoledronic acid treatment appears to be promising in men with low BMD receiving GnRH-a treatment.

Expression of three gonadotropin subunits and gonadotropin receptor mRNA during male-to-female sex change in the cinnamon clownfish, Amphiprion melanopus

To quantify the sex-change progression from male to female in the cinnamon clownfish, Amphiprion melanopus, we divided gonadal development into three stages (I, mature male; II, male at 90days after removal of the female; and III, mature female), and the expression of GTH subunits and GTH receptors during each of these stages was investigated. The mRNA of the three GTH subunits and their receptors increased with progression from male to female. To understand the effect of gonadotropin-releasing hormone (GnRH) on this progression, we examined expression of genes encoding the GTH subunit mRNA in the pituitary and the GTH-receptor mRNA in the gonads in addition to investigating changes in plasma E2 levels after GnRH analogue (GnRHa) injection. GnRHa treatment increased mRNA expression levels of these genes, as well as plasma E2 levels, indicating that GnRH plays an important regulatory role in the brain-pituitary-gonad axis of immature cinnamon clownfish.

Bone density in children treated with gonadotropin-releasing hormone analogs for central precocious puberty

Estrogens, growth hormones and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with gonadotropin-releasing hormone analogs (GnRHa), leads to a situation of hypoestrogenism by reducing sex-steroid levels, which, theoretically, may have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density during GnRHa treatment has been shown, but GnRHa treatment in patients with central precocious puberty does not seem to impair the achievement of normal peak bone mass at adult height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better peak bone mass achievement.

GnRH analogue treatment and decrease of bone mass density (BMD) in a patient with Osteogenesis Imperfecta (OI) and Central Precocious Puberty (CPP)

perfecta (OI), with the aim of improving height velocity, bone mineral density (BMD) and projected bone areas.Study design: We observed a randomized population of patients: 30 pre-pubertal children (14 boys and 16 girls) suffering from OI (type I, IV and III), already receiving treatment with Neridronate. After an observational period of 12 months during ongoing Neridronate treatment, the patients were randomized into two groups: Group A, 15 children (7 boys and 8 girls) were treated for 12 months with GH and Neridronate; Group B, 15 (7 boys and 8 girls) continued Neridronate alone. We evaluated auxological parameters, number of fractures, bone age (BA), bone metabolic parameters and bone mass measurements with DXA (lumbar column and radius), in the year before and throughout the GH treatment. Results: Growth velocity was significantly higher during GH treatment in Group A vs Group B and vs pre-treatment period (p<0.05), with no difference in Bone Age advancement. The number of fractures did not increase during GH treatment. IGF-I levels were in the low-normal range before therapy and increased significantly after 12 months in Group A vs Group B and vs pre-treatment (p<0.05). Bone mineral density (BMD) at the lumbar column (L2L3L4), distal radius and ultra distal radius (Δ % BMD), and the projected area of lumbar column increased significantly in Group A vs Group B (p<0.05). With a complete molecular characterization in both type I collagen genes (COL1A1 and COL1A2 ), we differentiate between qualitative and quantitative collagen synthesis defects. Patients with quantitative defects had a higher, although not significant, response to GH treatment in terms of growth velocity and BMD. Conclusions: In patients with Osteogenesis Imperfecta the combined GH Bisphosphonate treatment may give better results than Bisphosphonate treatment alone in terms of growth velocity, higher BMD at the lumbar column and wrist, lumbar column projected area, especially in patients with quantitative collagen synthesis defects.

Can the TW3 Bone Age Determination Method Provide Additional Criteria for Growth Hormone Treatment in Adopted Girls with Early Puberty?

Background/Aims: Gonadotropin-releasing hormone analogues (GnRHa) are the accepted treatment of idiopathic central precocious puberty. As it has been found that growth velocity may be decreased with GnRHa treatment, clinical trials with GnRHa combined with growth hormone (GH) have been carried out. In a recent study 46 adopted girls with early or precocious puberty were randomly assigned to treatment with either GnRHa or GnRHa combined with GH, and followed to final height (FH). It was found that FH was significantly higher in the combined treatment group, 158.9 compared with 155.8 cm in the GnRHa treated group. In order to select the patients who could benefit from added GH, predictions of FH at the start of treatment according to the methods of bone age determination of Greulich-Pyle (GP) and Tanner-Whitehouse 2 (TW2) were compared. It was found that the GP method was the most useful method for patient selection. Recently, a revision of the Tanner-Whitehouse method, named Tanner-Whitehouse 3 (TW3), has been developed. The present study examined the usefulness of the TW3 method in selecting suitable patients for combined treatment. Method: The TW3 method bone age determinations of the 46 girls were compared to the GP and TW2 method determinations, using the differences between actual FH and predicted adult height (PAH). Beside accuracy of prediction of FH, the criteria of efficiency of selection and replicability were applied in the comparison. Results: We found that the GP method, also when compared to the TW3 method, gave the most accurate prediction of the FH on only GnRHa treatment. This gives the best ground for selection of patients who can benefit from combined treatment. The GP method was also the most efficient in selecting patients, i.e., it could select the least number of patients that needed the combined treatment. The only drawback of the GP method was that it requires an experienced pediatric radiologist. Automated methods are being developed and may soon facilitate the use of the GP method for those less experienced. The FH after combined treatment could be predicted with an equation including PAH GP as well as PAH TW3 as variables. Conclusion: The GP method remains the most useful method for selection of those patients who will benefit most from the addition of GH to GnRHa in the treatment of idiopathic central precocious or early puberty. FH prediction after combined treatment requires PAH GP as well as PAH TW3.

Two Cases of Precocious Puberty Associated with Hypothalamic Hamartoma

Hypothalamic hamartoma (HH) is a congenital malformation diagnosed based on magnetic resonance imaging (MRI) and histological findings; it is often associated with central precocious puberty (CPP), gelastic seizures, abnormal behavior and mental retardation. In the present paper, we report our retrospective hypothesis that there is a relationship between symptoms and therapy, as well as the treatment for HH, and describe two cases of HH associated with CPP. Both cases had sessile masses located in the interpeduncular cistern, with extension to the hypothalamus on MRI (1.2 × 1.5 cm and 2.0 × 2.5 cm, respectively). The first case had intractable seizures, while the second had no seizures with paroxysmal discharge. In both patients, the hamartomas were partially removed, by γ-knife and surgical operation in the first case and surgically in the second, and a gonadotropin releasing hormone (GnRH) analogue was prescribed. One case showed improvement of both intelligence quotient (IQ) score and seizures, and the other showed improvements in IQ and abnormal behavior. It was difficult to determine any topology/symptom relationships. Surgery and GnRH analogue treatment can alleviate seizures, abnormal behavior and mental retardation associated with HH.

Effect of gonadotropin releasing‐hormone analogue and human chorionic gonadotropin on milt characteristics and gonadal steroids in yellowfin bream, Acanthopagrus australis (Sparidae)

Adult yellowfin bream (Acanthopagrus australis) were captured from the wild and maintained in outdoor tanks until the onset of the natural spawning season (May ‐ June). Three replicate trials were conducted to examine the effects of gonadotropin releasing‐hormone analogue (GnRHa) and human chorionic gonadotropin (hCG) on milt characteristics and gonadal steroid levels. Spermiating males were injected intraperitoneally with either saline solution (control) or a single dose of GnRHa (25, 50, 75, 100 μg kg−1) or hCG (250, 500, 750, 1000 IU kg−1). Milt and blood samples were collected before hormone administration (0 h) to examine initial reproductive status, and at 6, 24, and 48 h post injection (p.i.) to assess the effects of hormone treatment. There was a progressive increase in the reproductive condition of fish held throughout the experimental period, with increases in milt volume and sperm concentration over time, and a corresponding fall in the duration of sperm activity. Treatment with saline solution or hCG did not significantly alter reproductive parameters. Treatment with GnRHa at a dose of 100 μg kg−1 significantly increased milt volume and reduced sperm concentration at 48 h p.i. The cumulative number of sperm collected over the 48 h sample period was also elevated. The duration of sperm activity was unaffected by hormone dose or type. All GnRHa treatment groups had elevated levels of 11‐ketotestosterone (11‐KT) at 24 and 48 hp.i. Plasma testosterone levels did not change with treatment. The increase in milt volume and cumulative sperm number in the 100 μg kg−1 group coupled with the elevated levels of 11‐KT throughout this period suggest gonadotropin‐dependent production of 11‐KT as a mediator of spermiogenesis, but not spermiation in yellowfin bream. The lack of response to hCG may be explained by low potency of the hormone in yellowfin bream during the early spawning season.

The Efficacy and Safety of Gonadotropin-Releasing Hormone Analog Treatment in Childhood and Adolescence: A Single Center, Long-Term Follow-Up Study

The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function. Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated). FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects. BMI values of GnRHa-treated and nontreated subjects in groups A and C were comparable, whereas in group B, a higher BMI was found in subjects treated only with GH. Nontreated patients with ICPP had greater maximal ovarian volumes, higher LH and LH to FSH ratio, and more severe hirsutism than GnRHa-treated ones. Menstrual cycle characteristics were not different between treated and nontreated subjects. The prevalence of polycystic ovary syndrome in treated and untreated girls with ICPP was comparable, whereas in the entire cohort, it was 11.1% in GnRHa treated and 32.1% in the untreated (P = 0.02). Girls treated in childhood with GnRHa have normal BMI, BMD, body composition, and ovarian function in early adulthood. FH is not increased in girls with ICPP in whom GnRHa was initiated at about 8 yr. There is no evidence that GnRHa treatment predisposes to polycystic ovary syndrome or menstrual irregularities.

Osmotic stress response is altered in leiomyoma cells

OBJECTIVE: Clinical treatment of leiomyomas with GnRH analogue produces a rapid reduction in leiomyoma volume. Rapid leiomyoma regrowth when GnRH treatment is withdrawn suggests the reduction in volume is due to transport of water, yet little is known about the response of leiomyoma cells to osmotic stress. Nuclear factor of activated T cells 5 (NFAT5) is the key osmo-sensing transcription factor in human cells. Our goal was to characterize osmosensing via NFAT5 in leiomyoma cells. DESIGN: Prospective, human model experiments MATERIALS AND METHODS: Osmotic stress was induced by culturing immortalized human leiomyoma and myometrial cells in DMEM-10% FBS with additional osmolytes of NaCl at 25, 50 or 100 mM for 8 hours. Proliferation assays were performed by the sulforhodamine B method. Apoptosis was assessed by caspase 3/7 activity assay. Expression of NFAT5 in tissue and cells was determined with qRT-PCR and western blot analysis. RESULTS: Leiomyoma cell growth was inhibited 18% at 50 mM NaCl compared to 48% in myometrial cells (p<0.05), consistent with altered osmosensing in leiomyoma cells. This finding was not due to apoptosis, as evidenced by no change in caspase activity. NFAT5 transcripts were increased in leiomyoma 1.5 fold ± 0.19 compared to myometrium in 4 of 7 patient samples (p<0.05). Concentration dependent upregulation of NFAT5 mRNA was observed in osmotically stressed leiomyoma cells. At 50mM NaCl, NFAT5 transcripts were increased 2.5-fold compared to control. CONCLUSIONS: Leiomyoma cells were more resistant to changes in osmotic stress than myometrial cells, suggesting dysregulation in osmotic signaling in leiomyomas. This change was accompanied by differential expression of NFAT5 in leiomyoma tissue. Altered osmotic signaling in leiomyoma cells suggests a central role for water regulation in the rapid change of leiomyoma volume with GnRH analogue treatment.

GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective, randomized, multicenter study

To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding. Multicenter, prospective, randomized, clinical study. Tertiary-care university hospitals. Thirty-nine consecutive patients with submucous myomas graded as G0 or G1 according to the European Society for Gynecological Endoscopy classification (myoma size 10-35 mm). Patients were randomized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma. Operating times, fluid absorption, difficulty of the operation, surgeon satisfaction with the procedure, intra- and postoperative complications, postoperative pain, and patient satisfaction were recorded. Patients treated with GnRH analogue had significantly shorter operative times (15.9+/-3.1 minutes vs. 21.3+/-4.0 minutes) and significantly reduced fluid absorption (378+/-137 mL vs. 566+/-199 mL) compared with no preoperative medical treatment. Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group. Patient satisfaction was similar in the two groups. GnRH analogue treatment before hysteroscopic resection of G0-G1 10-35 mm submucous myomas was effective in reducing operative times, fluid absorption, and difficulty of the procedure.

Quantitative mRNA expression of sox3 and DMRT1 during sex reversal, and expression profiles after GnRHa administration in black porgy, Acanthopagrus schlegeli

We cloned full-length sox3 cDNA from testis of black porgy, Acanthopagrus schlegeli. Black porgy sox3 cDNA consists of 897 base pairs (bp) and encodes a protein of 298 amino acids. We have investigated the expression pattern of sox3 and DMRT1 mRNA during the sex-reverse process from male to female (immature testis, mature testis, testicular portion of mostly testis, ovarian portion of mostly testis, testicular portion of mostly ovary, ovarian portion of mostly ovary and ovary). The expression of sox3 and DMRT1 mRNA was high in mature testis of black porgy during sex-reverse process. In a histological analysis, testicular portion of gonad was degenerated and the ovary portion was increased during sex reversal from male to female, and then oocytes were increased in ovary. Also we examined the expression of sox3 and DMRT1 mRNA after gonadotropin-releasing hormone analogue (GnRHa) treatment in immature black porgy. The expression of sox3 and DMRT1 mRNA was increased after GnRHa treatment (in vivo and in vitro experiment) in immature black porgy. Therefore, we concluded that sox3 and DMRT1 were involved in the development of testis than ovary in black porgy.

Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA)

Several studies showed a decrease in height velocity during GnRH analogue (GnRHa) treatment. No information is available on GH levels during GnRHa treatment in short SGA girls. To study overnight GH profiles and IGF-I and IGFBP-3 levels in girls with Tanner stage 2 and stage 3, before and after 3 months of GnRHa treatment, and to compare levels with those found in prepubertal short SGA girls. Twenty-four pubertal and 16 prepubertal short SGA girls. After baseline overnight GH profiles, pubertal girls received leuprorelide acetate depots of 3.75 mg subcutaneously every 4 weeks. GH, IGF-I and IGFBP-3 levels. At baseline, GH levels were comparable to levels found in prepubertal short SGA girls and IGF-I and IGFBP-3 SDS were significantly below the population mean. After 3 months of GnRHa treatment, AUC(0) (P = 0.02), mean (P = 0.02) and maximum GH levels (P = 0.008) had significantly decreased. Mean GH levels were significantly lower than in prepubertal short SGA girls (P = 0.03). Eight girls with more than 40% decrease in mean GH levels also had a significantly greater decrease in IGF-I and IGFBP-3 levels. Mean and maximum GH levels at baseline correlated significantly with those after 3 months of GnRHa treatment. Short SGA girls lack the normal increase in GH levels seen in puberty and have reduced IGF-I and IGFBP-3 levels, which might explain their reduced pubertal growth spurt. GnRHa treatment led to a significant reduction in GH levels. Therefore, combining GnRHa treatment with GH treatment might improve adult height of short SGA girls.

17β-Hydroxysteroid dehydrogenase-3 deficiency: From pregnancy to adolescence

Aim of this study is to report on basal clinical phenotype and follow up after diagnosis, of patients with 17beta-hydroxysteroid-dehydrogenase type 3 (17beta-HSD3) deficiency in Italy. Pediatric Endocrine Departments, University Hospitals. The cases of 5 Italian subjects affected by 17beta-HSD3 deficiency are presented in this study. Laboratory and genetic assessment. Gonadectomy and female sex assignment (4 patients) or GnRH analog therapy to regress puberty and gender identity disorder (1 patient). Presentation lasted from pregnancy (pre-natal diagnosis of a 46,XY fetus with female external genitalia) to infancy (inguinal hernia containing testes/clitoromegaly) and adolescence (virilisation). All subjects but one (subject 1, Central-Northern Italy) were from small areas of Southern Italy. Endocrine data (baseline and/or stimulated testosterone/ Delta4-androstenedione ratio) were informative. Two girls were homozygous for 17beta-HSD3 gene mutations (G289S/G289S; R80W/R80W), while the others were compound heterozygous (IVS325+4 A>T/A203V; L212Q/M235V; R80W/A235E). Four patients were confirmed as females and were well-adjusted with assigned sex; gender identity disorder improved during treatment with GnRH analog in the last subject. 17betaHSD3 deficiency may present from pregnancy to puberty for different clinical issues. Albeit testosterone/Delta4-androstenedione ratio represents the most accurate endocrine marker to diagnose the disorder, hCGstimulation is mandatory in pre-puberty. Molecular analysis of 17beta-HSD3 gene should be performed to confirm the diagnosis. Temporary GnRH analog treatment may regress gender identity disorder and provide time to confirm or change the birth sex assignment. Female individuals seems to be compliant with their sex, providing that virilisation does not occur. In Italy, the disorder seems to be more prevalent in the Southern regions and shows genetic heterogeneity.

Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone (GH) profiles and fasting insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels after 3 months of GnRHa treatment with those at baseline. Methods: After measurement of baseline overnight profiles and IGF-I and IGFBP-3 levels, 14 short pubertal SGA boys received leuprorelide acetate depots of 3.75 mg subcutaneously, every 4 weeks. Results: At baseline, mean GH levels were comparable with those of controls, whereas IGF-I and IGFBP-3 standard deviation scores (SDS) were significantly lower than zero SDS. After 3 months of GnRHa treatment, all boys showed clinical arrest of puberty. The area under the curve above zero, mean and maximum LH and FSH had significantly decreased to prepubertal levels. Peak LH during the GnRH agonist test, however, indicated insufficient pubertal suppression in 43% of boys. Overnight GH profile characteristics and IGF-I and IGFBP-3 levels did not significantly change. Conclusions: Puberty was sufficiently suppressed by GnRHa treatment, as shown by the prepubertal LH and FSH profiles. After 3 months of GnRHa treatment, overnight GH profile characteristics had not significantly changed, reflecting that GH levels are comparable for prepubertal and early pubertal boys.

Initial growth deceleration during GnRH analogue therapy for precocious puberty

To compare the efficacy of goserelin and leuprolide on initial deceleration of growth and weight gain during the first 12 months of GnRH analogue treatment for precocious puberty. Retrospective cohort analysis. Forty children with precocious puberty treated with either goserelin or leuprolide (33 females, mean age 7.3 and 7.7 years, respectively, at the start of treatment). The primary outcomes were baseline-to-6-months and 6-months-to-12-months change in height standard deviation score (SDS) and body mass index (BMI). Relative tall stature was calculated as the difference between height SDS and mid-parental height (MPH) SDS at baseline. Goserelin and leuprolide were associated with similar suppression of serum LH during the first 12 months of treatment (P = 0.62). Greater relative tall stature was strongly associated with more advanced bone age, greater BMI SDS and with greater reduction in height SDS in the first 6 months. Adjusted for relative tall stature, goserelin therapy was associated with significantly greater suppression of growth than leuprolide (P = 0.025) in the first 6 months of treatment, with no subsequent change in the second 6 months. A similar, significant increase in BMI was seen with both analogues. Both GnRH analogues were associated with effective biochemical suppression of puberty; however, goserelin was more effective at reducing linear growth during the first 6 months. Relative tall stature was a major determinant of the initial response to treatment.

Body Mass Index and Body Composition in Adolescents Treated with Gonadotropin-Releasing Hormone Analogue Triptorelin Depot for Central Precocious Puberty: Data at Near Final Height

Background/Aim: In children with central precocious puberty (CPP), gonadotropin-releasing hormone (GnRH) analogue treatment has been associated with an increase in body mass index (BMI). We evaluated BMI and body composition in adolescents treated with GnRH analogue at their near final height to assess the long-term effects of therapy on these parameters. Patients and Methods: We studied 20 patients (14.8 ± 1.6 years; 17 females) previously treated with triptorelin depot for CPP (3.75 mg/28 days) from 8.1 ± 0.8 to 11.5 ± 0.8 years. 23 healthy adolescents with normal onset of puberty (14.7 ± 2.1 years, 19 females) were the controls. BMI and body composition (dual-energy x-ray absorptiometry) were assessed. Results: Patients reached their near adult height (–0.5 ± 1.1 standard deviation score (SDS)); the girls were menstruating and the majority (15/17) had regular cycles, the boys showed normal testicular function. BMI was unchanged from the start of GnRH analogue therapy (0.4 ± 1.0 SDS) to near adult height (0.2 ± 1.0 SDS, p = NS vs. 0). Total fat mass (TFM) was significantly increased (16,144 ± 8,065 g; controls 10,712.1 ± 4,120.4 g, p < 0.02); glucose homeostasis and lipid profile corresponded to reference ranges. Conclusions: GnRH analogue therapy did not show long-term detrimental effects on BMI, but it may increase TFM, suggesting that body composition should be monitored till adulthood.

Effect of GnRH analogue on the bone mineral density of precocious or early pubertal girls

Purpose:Treatment of precocity with gonadotropin releasing hormone analogue (GnRHa) might theoretically exert a detrimental effect on the bone mass during pubertal development. We investigated the short-term changes in bone mineral density (BMD) during GnRHa treatment and the enhancement in the changes with the co-administration of GnRHa and human growth hormone (hGH). Methods:Forty girls with precocious or early puberty who were using GnRHa for more than 1 year were enrolled. Of them, 14 concurrently received hGH. Lumbar bone mineral density was measured before and after the treatment, and bone mineral density-standard deviation scores (BMD-SDSs) were compared according to chronologic age (CA) and bone age (BA), as well as according to the administration of GnRHa alone (Group I) or the co-administration of hGH and GnRHa (Group II). Results:BMDs before and after treatment were in the normal range according to CA but were significantly lower according to BA (P

A Case Report of an Endometrial Stromal Sarcoma in a Patient with Infertility Revealed After Hysteroresectoscopy

It is important to remove endometrial polyps, which are well-known as a cause of implantation failure, from infertile female patients. Transcervical resection (TCR) is a treatment modality developed for endometrial polyps. We report a case involving a female with infertility due to an endometrial polyp which was shown to be an endometrial stromal sarcoma (low grade) after TCR. The patient was a 30-year-old nulligravida. She had no significant medical history, and had been married for 13 months. Before seeking evaluation at Fukushima Medical University Hospital, she underwent a myomectomy under laparotomy at another hospital. According to the pathology report, the fibroid was a cellular myoma with no evidence of malignancy. However, an endometrial polypoid lesion was noted during hysterosalpingography after the follow-up examination. On transvaginal ultrasonography, the solitary polyp was 22 mm in diameter with a cystic component. Before surgery, she received GnRH analog treatment for 1 month. Based on the resected specimen, the polyp was highly suspected to be an endometrial stromal sarcoma, therefore she was informed that a hysterectomy with bilateral oophorectomy and pelvic lymphadenectomy was recommended for radical treatment. Two months later, the surgery was performed, and it was finally diagnosed that the uterine fibroma was composed of an endometrial stromal sarcoma (low grade). She was treated with oral medroxyprogesterone acetate without evidence of recurrence.