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Approximately 11% of patients with breast cancer (bca) are diagnosed before menopause, and because in most of those patients the tumour expresses a hormone receptor, treatment with endocrine interventions can be applied in any setting of disease (early or advanced). In the past, hormonal treatment consisted only of the estrogen receptor modulator tamoxifen, associated with luteinizing hormone&ndash, releasing hormone (lhrh), more recently, aromatase inhibitors (ais) have come into widespread use. The ais interfere with the last enzymatic step of estrogen synthesis in which androgens are converted into estrogens. Initially, the ais were used alone in postmenopausal patients to prevent disease recurrence, but together with lhrh analogs, they can be used in premenopausal patients to produce better estrogen suppression than can be achieved with tamoxifen plus a lhrh analog. Using a systematic review of the scientific literature (prospective and retrospective studies), we set out to assess the efficacy of ais compared with other endocrine therapy in various disease settings (neoadjuvant, adjuvant, metastatic).

Permintaan ikan belida cukup tinggi untuk memenuhi kebutuhan konsumsi dan bahan baku olahan makanan yang masih mengandalkan tangkapan dari alam. Tingginya eksploitasi mengakibatkan populasi ikan dari tahun ke tahun semakin berkurang dan terancam punah. Teknologi pembenihan ikan belida dengan penggunaan hormon diduga dapat meningkatkan produksi larva untuk keperluan budidaya. Penelitian dilakukan untuk mengevaluasi performasi pemijahan ikan belida secara alami dan buatan melalui induksi hormon HCG dan LHRH analog. Pemijahan alami dan buatan dilakukan menggunakan induk betina sebanyak enam ekor dan jantan tiga ekor (rasio 2:1). Induk yang digunakan berukuran panjang 46 ± 5 cm dan bobot 2.209 ± 623 g. Pemijahan buatan dilakukan dengan induksi hormon HCG dosis 500 IU/kg dan LHRH analog dosis 0,5 mL/kg. Penyuntikan HCG dan LHRH diberikan dengan interval 24 jam. Hasil penelitian menunjukkan pada pemijahan buatan (induksi hormon) diperoleh induk yang memijah sebanyak dua ekor dengan nilai diameter telur (3,1 ± 0,3 mm); fekunditas (282-907 butir); derajat pembuahan (21%-40%); derajat penetasan (56%-75%); dan sintasan (30%-50%); sedangkan pada pemijahan alami diperoleh satu ekor induk yang memijah dengan nilai diameter telur (3,5 ± 0,3 mm); fekunditas (1.616 butir); dan derajat pembuahan (86,7%); selama tiga bulan pengamatan secara intensif dengan frekuensi pemijahan enam kali. Aplikasi teknologi pemijahan dengan menggunakan induksi hormon dapat menghasilkan produk larva pada ikan belida.The demand for fish consumption of Clown Knifefish is considerably high. However, the fish supply for consumption and processed food still relies on wild-caught. Such exploitation has decreased the population of Clown Knifefish to a point that it can become an endangered species. Efforts on the breeding technology of Clown Knifefish through natural and artificial propagation using of hormones have shown promising results. The current study was conducted to evaluate the performance of Clown Knifefish in natural and artificial spawning conditions using the induction of HCG hormone and LHRH analogues. The natural and artificial spawning treatments were conducted using six fish females and three fish males (a ratio of 2:1). The average Broodstocks’ size was 46 ± 5 cm in length and 2,209 ± 623 g in weight. The artificial spawning was conducted with HCG hormone induction (dose of 500 IU/kg body weight) and LHRH analogue (dose: 0.5 mL/kg). HCG and LHRH injections were given within 24 hours interval. The results showed that the artificial spawning (hormone induction) had successfully caused two broodstock to spawn producing eggs with the diameter of 3.1 ± 0.3 mm; fecundity of 282-907 eggs; fertilization rate of 21%-40%; hatching rate of 56%-75%; and survival rate of 30%-50%. In the natural spawning, one broodstock had spawned with the egg diameter of 3.5 ± 0.3 mm; fecundity of 1,616 eggs; and fertilization rate of 86.7%. This study concludes that spawning technology applications using hormonal induction can increase the production larvae of Clown Knifefish broodstock.

To improve the final height of short children who enter puberty at short stature, twenty-one boys who entered puberty shorter than 130 cm and twelve girls who entered puberty shorter than 125 cm were treated with a combination of GH and LHRH analog. Combined GST and GH treatment was started in boys and girls at a mean age of 11.78 (±0.82) years and 10.54 (±1.08) years, mean height of 130.0 (±4.4) cm and 122.6 (±3.2) cm, and mean height SD of -2.34 (±0.61) SD and -2.78 (±0.99) SD respectively. During the combination treatment, bone age decelerated after a bone age of 11.5 years in boys and 10 years in girls, and height velocity did not decelerate but remained at from 3 cm/year to 5 cm/year for a longer period. As a consequence of the treatment, the height SD score for bone age increased significantly. Seven boys and six girls discontinued LHRH analog treatment when the mean age was 17.11 (±1.15) years after a mean treatment period of 4.96 (±1.37) years for boys and when the mean age was 13.89 (±1.79) years after a mean treatment period of 3.21 (±1.52) years for girls. The mean height was 155.1 (±3.1) cm for boys and 143.3 (±3.0) cm for girls and their predicted adult height was 169.8 (±2.5) cm for boys and 155.8 (±3.1) cm for girls at the cessation of the combination treatment. All except one girl in our study will have achieved greater than the standard height gain during puberty. Although combined GH and LHRH analog treatment can improve the final height of short children by increasing pubertal height gain, the combination treatment seems more effective in boys than in girls.

The bone mineral density (BMD) of the 2nd metacarpal bone of the left hand was measured in 14 children with complete GH deficiency (CGHD) and 21 children with partial GH deficiency (PGHD) by the digital image processing (DIP) method. In the pretreatment patients, mean BMD in CGHD was significantly lower than that in normal children. The BMD standard deviation (SD) score in the patients with CGHD who had started the GH treatment before 10 years of age increased by approximately 1.5 SD during GH treatment, while that in the patients with PGHD did not change significantly. Since BMD did not show a pubertal increase in the patients who received combined GH and LHRH analog treatment, their BMD SD score decreased by approximately 1.5 SD. The data demonstrate that GH influences BMD, and the level of BMD in patients with GHD should be followed in a longitudinal observation.

Clinical variables that influence final height were analyzed in 27 girls with central precocious puberty treated with LHRH analog (TAP-144-SR: leuprorelin acetate). The patients were treated for a mean treatment period of 210.4 weeks. Plasma IGF-I levels did not change significantly during treatment. The predicted final height by projected height standard deviation score (SDS) for bone age at final estimation correlated positively with the average growth velocity during LHRH analog treatment. The mean growth velocity showed a significant negative correlation with the mean dose of LHRH analog; such a tendency was also clearly observed in patients who began to receive treatment after the age of 6 years. Although estradiol levels did not show any correlation with height velocity because of the low sensitivity of estradiol measurement, changes in plasma estradiol levels may contribute to changes in growth velocity, especcially in patients of pubertal bone age. To improve the final height prognosis in precocious puberty, it is recommended that LHRH analog be used at the minimum effective dose to maintain growth velocity during treatment.

It has been reported that the final height in short children is strongly related to the height at the onset of pubertal development, and pubertal height gain in GH-treated children is not exceed the gain in normal children. Therefore, it is now the consensus that insufficient height at the onset of puberty leads to short final height. We have already demonstrated that the final height in GH-deficient children with spontaneous puberty with gonadal suppression therapy by medroxyprogesterone or cyproterone acetate was significantly taller than GHD with spontaneous puberty without gonadal suppression therapy. In this study, we treated short boys who started puberty at height shorter than 130 cm with combined GH and LHRH analog. Final height was predicted by the height SD score for bone age. Although pubertal growth spurt was not recognized in short children on combination treatment, bone age maturation over 11.5 years decelerated significantly to the rate of one year in three or four years. Even during this slow bone maturation period, growth velocity remained at 4 cm/year due to GH treatment. Therefore, height SDS for bone age was improved in combination with the elongation of treatment period by the slow bone maturation. Some investigators recommend not to delay induction if puberty much beyond the normal age to avoid psychological problems and ennuchoid proportion in these children. When we explained to our Japanese patients the chance of increasing the final height with gonadal suppression treatment and the risk of delaying the pubertal development, almost all children preferred taller final height to pubertal development and they did not experience much psychological trouble. The differences in social and cultural circumstances do, however, influence patients' preferences.

LBA505 Background: Premature ovarian failure (POF) is a common toxicity of CT. Risk depends on type and amount of CT, age, and perhaps ovarian cycling at the time of CT. POEMS is a SWOG-coordinated phase III randomized study to evaluate whether LHRH analog administration with CT for early-stage breast cancer (BC) would reduce POF. Methods: Premenopausal patients (PT) age .05). POF rates were 22% in the standard arm and 8% in the GN arm (OR=0.30, 95% CI: 0.10-0.87, p=.03 [unadjusted analysis]; OR=0.36, 95%CI: 0.11-1.14, p=0.08 [adjusted logistic regression analysis]). In a sensitivity analysis defining 2-year POF more liberally as either amenorrhea or elevated FSH, 45% in the standard arm and 20% in the GN arm had POF (OR=0.29, 95% CI: 0.12-0.70, p=.006). There were 13 pregnancies in the standard arm and 22 in the GN arm (OR=2.22, 95% CI: 1.00-4.92, p=.05). DFS and OS were better in the GN arm (Cox regression, including stage: HR=0.49, 95% CI: 0.24-0.97, p=.04; HR=0.43, 95% CI: 0.18-1.00, p=.05, respectively). Conclusions: LHRH analog administration with CT was associated with less POF and more pregnancies. In an exploratory analysis, GN use in premenopausal ER-negative BC was associated with improved DFS and OS. Clinical trial information: NCT00068601.

Effects of Lhrh-Analog (Lhrh-A)-Induced Pubertal Delay in Growth Hormone Deficient Children Treated With Growth Hormone: Preliminary Results of A Randomized, Placebo-Controlled Trial. 1

To determine the effect of rhIGF-I treatment plus LHRH analog on growth velocity and bone maturation in a pubertal patient with growth hormone insensitivity syndrome (GHIS), we treated an 18.5-year old mid-pubertal boy with GHIS with rhIGF-I 100 ug/kg twice daily plus LHRH analog (deslorelin) 4 ug/kg/day. Pretreatment height was 111.2 cm (−10 S.D.), growth rate was 4.1 cm/year, bone age 14.5 years, peak plasma LH 32.1 IU/L, peak FSH 7.2 IU/L and testosterone (T) 342 ng/dL. Serum IGF-I increased from an undetectable level at baseline to 108 ng/mL at 1 h post administration. GH secretion, measured q 30 min for 24 h, was suppressed from 1 h to 12 h post IGF-I administration. IGFBP-3 was unchanged. After three months of therapy, growth rate had increased from 4.1 to 8.7 cm/year, bone age was unchanged, gonadotropins were suppressed by the deslorelin, and T had fallen from 342 to 53 ng/dL. We conclude that rhIGF-I therapy in combination with LHRII analog can increase growth rate in pubertal patients with GHIS. Longer follow-up is needed to assess the long-term outcome of rhIGF-I plus LHRH analog treatment on growth velocity, and bone age advancement, and adult height.

Twenty-five male patients with idiopathic hypogonadotropic hypogonadism were treated with 5μg of an LHRH analog (D-Leu6-Des-Gly10-LHRH-ethylamide) intramuscularly for one month. The FSH and LH responses (quantitated as cumulative response areas) to acute LHRH intravenous administration (100 μg) were evaluated before and after each week of treatment. The patients were randomly divided into two groups: group A (16 patients) was treated every day; group B (nine patients) was treated every other day. Each group was divided into two subgroups (1 and 2), according to the degree of pretreatment LH response impairment. Patients in the first subgroup had a pretreatment cumulative response area greater than 3 SD below the mean for normal males. Patients in the second subgroup had a response less than 3 SD below the mean for normal males. Daily treatment produced a significant and progressive increase in LH response in subgroup A-1, but in the second subgroup (A-2) there was a maximal increase after the first and second week, with a subsequent decline. Alternate-day treatment, on the other hand, produced a significant and progressive increase in LH response in all patients from subgroups B-1 and B-2. Both daily and alternate-day treatments induced an initial increase in FSH response during the first week, followed by a progressive decline in all the groups. Finally, there was a lack of response to either form of treatment with regard to testosterone secretion and spermatogenesis. The findings indicate that LH response to LHRH analog differed depending on the degree of pretreatment pituitary impairment and the course of therapy followed.

In children with isolated GH deficiency, not treated early with hGH, final height may be compromised by puberty initiation. Previous attempts to inhibit pubertal development in such subjects by cyproterone acetate failed to improve final height. We attempted to inhibit puberty with LHRH analog in two adolescents with isolated GH deficiency, aged 14.5 years (case I) and 12 years (case II) respectively, in order to prolong the growth period and possibly improve final height. One received LHRH analog by nasal spray and the other IM monthly injection (TRp6 microcapsule). hGH was given IM, 4IU 3 times weekly. The most pertinent data are listed below: Although it is too early to predict the efficacy of such intervention, a ratio of ΔHt. age to ΔB. age greater than 2 suggests that improvement in final height might be achieved. This however requires confirmation by longer follow-up period.