Triptorelin Research Articles

Efficacy of leuprolide acetate versus triptorelin pamoate administered every 3 months for treatment of central precocious puberty

Efficacy of leuprolide acetate versus triptorelin pamoate administered every 3 months for treatment of central precocious puberty

A Phase3, Open-Label, Single-Arm Trial of the Efficacy and Safety of Triptorelin 6-Month Formulation in Chinese Children with Central Precocious Puberty.

This phase3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP). In this open-label study (NCT05029622), Chinese children (girls < 9years, boys < 10years) received two doses of triptorelin pamoate 22.5mg (day1 and month6). Primary endpoint was the proportion at month6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline. Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5-9] years). At month6, all patients had LH suppression; this was maintained at month12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months3 to 12had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month6 and 12, respectively; all boys had regression or stable genital development until month12. Compared with baseline (9.82cm/year), mean growth velocity was 5.88cm/year at month6 and 5.17cm/year at month12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month6 and 12 versus baseline, while 75.0% of boys showed stable testicular volume versus baseline. Thirteen patients (19.7%) had 22 drug-related treatment emergent adverse events (TEAEs); no grade ≥ 3 TEAEs were reported. The efficacy and safety profile of triptorelin 6-month PR in Chinese children with CPP was consistent with data previously reported in non-Chinese children with CPP, supporting this as a viable treatment option for Chinese children with CPP. Trial registration:ClinicalTrials.gov identifier, NCT05029622.

Long-Acting Gonadotropin-Releasing Hormone Analogues for Central Precocious Puberty, Including 45-Mg 6-Month Subcutaneous Leuprolide Acetate: Use for Treatment and Treatment Monitoring

Plain Language SummaryThe gonadotropin-releasing hormone analogue (GnRHa) stimulation test has historically been used for diagnosing and monitoring treatment efficacy in children with central precocious puberty (CPP). However, this test is not always practical due to costs related to lengthy hospital or clinical testing, and additional injections that may negatively impact the child’s therapeutic experience. Therefore, alternative methods of assessing therapeutic efficacy would be valuable. This manuscript presents an overview of the studies supporting the suitability of therapeutic dosing of CPP medications (intramuscular [IM] leuprolide acetate [LA], IM triptorelin pamoate, and subcutaneous [SC] LA) for treatment monitoring. Four studies of injectable CPP medications have demonstrated that these therapies achieved similar stimulated luteinizing hormone (LH) levels compared to a traditional GnRHa stimulation test. However, the effect of SC LA (approved by the US FDA for treatment in May 2020) on LH levels has not been directly compared to those measured as part of a traditional stimulation test. As several studies have shown that SC LA has similar efficacy on the physical characteristics of puberty as IM LA, we postulate that therapeutic SC LA may also be used to monitor the response to CPP treatment, in place of a traditional GnRHa stimulation test.

Long-term efficacy of a triptorelin 3-month depot in girls with central precocious puberty.

Three-month gonadotropin-releasing hormone agonists (GnRHas) are expected to achieve better compliance in patients with central precocious puberty (CPP) compared to the monthly formulation. However, 1-month depot remains the dominant choice for conventional treatment worldwide. Our study aimed to investigate the long-term efficacy of a 3-month GnRHa for CPP treatment. In this retrospective study, 69 Korean girls with CPP were prescribed either triptorelin pamoate (TP) 3-month depot (n=29) or triptorelin acetate (TA) 1-month depot (n=40) and were followed for 1 year after the end of treatment. Auxological, radiological, and biochemical data were collected every 6 months. Baseline characteristics were similar between the 2 groups. In the TP 3-month depot group, 27 of 29 patients (93.1%) exhibited suppressed luteinizing hormone level (below 2.5 IU/L) after 6 months of treatment, and this suppression level was reserved until the final injection. The degree of bone age advancement in the TP 3-month depot group decreased from 1.8±0.4 years at the start of treatment to 0.6±0.5 years at 1-year posttreatment. The gain in predicted adult height (PAH) 1 year after the end of treatment was similar between the TP 3-month and TA 1-month depot groups (5.2±3.1 and 5.3±2.4 cm, respectively; p=0.875). A 3-month depot of triptorelin effectively inhibited gonadal and sex hormones, suppressed bone maturation, and increased PAH. For patient convenience, we suggest a 3-month GnRHa regimen as a promising CPP treatment option.

Testosterone nadir and clinical outcomes in patients with advanced prostate cancer: Post hoc analysis of triptorelin pamoate Phase III studies.

The objective of the study is to evaluate whether low nadir testosterone during treatment with triptorelin pamoate, a luteinising hormone-releasing hormone (LHRH) agonist, is associated with improved clinical outcomes in patients with advanced prostate cancer using a retrospective analysis of clinical trial data. Data were pooled from three prospective, 9-12-month Phase III studies of triptorelin monotherapy in patients with advanced prostate cancer (including NCT00751790). The serum testosterone concentration suppression targets evaluated were <0.35 nmol/L (<10 ng/dl), <0.7 nmol/L (<20 ng/dl), <1.7 nmol/L (<50 ng/dl) and ≥1.7 nmol/L. Overall survival (OS) and disease-specific survival (DSS) by testosterone suppression group were assessed by Kaplan-Meier analysis, with log-rank test. The time frame for the primary analysis was Days 1-518 (median OS follow-up 254 days [range, 29-518 days]) and for the sensitivity analyses was Days 1-262. Supplementary analyses combined the ≥0.7- to <1.7-nmol/L and ≥1.7-nmol/L groups. The sample size comprised 592 patients (most received triptorelin monotherapy; four reported concomitant androgen receptor-axis-targeted therapy). Nadir testosterones of <0.35, ≥0.35 to <0.7, ≥0.7 to <1.7 and ≥1.7 nmol/L were achieved by 96%, 3.2%, 0.34% and 0.17% of patients, respectively. Better OS with decreasing level of nadir testosterone was observed (p < 0.001) and this persisted after sensitivity/supplemental analyses (all p < 0.001). Differences in DSS with decreasing levels of nadir testosterone were not statistically significant in the primary analysis. Sensitivity/supplemental analysis showed better DSS with decreasing level of nadir testosterone (Days 1-262, p = 0.01; combined groups Days 1-518, p = 0.03; combined groups Days 1-262, p = 0.005). Low nadir testosterone achieved during treatment with the LHRH agonist triptorelin was associated with improved OS and DSS in patients with advanced prostate cancer.

Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase3, Open-Label, Single-Arm Study.

Triptorelin is available as 1- and 3-month prolonged-release (PR) formulations; at the time of the study, only the former was approved for central precocious puberty (CPP) in China. This study assessed the efficacy and safety of the triptorelin 3-month PR formulation in Chinese children with CPP. In this 12-month, prospective, open-label, multicentre, single-arm study (NCT04736602), Chinese children (mean age [standard deviation (SD)], 7.6 ± 0.8years) with CPP received triptorelin pamoate 15mg on day1 and at months 3, 6 and 9. The primary endpoint was the proportion with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 3IU/L after gonadotropin-releasing hormone [GnRH] stimulation) at month 3. Secondary endpoints included changes from baseline in hormone levels and clinical parameters, as well as safety assessments. Overall, 32 children were enrolled, including three boys. LH suppression to prepubertal levels (≤ 3IU/L) after GnRH stimulation was observed in 100%, 93.5% and 93.5% of participants at months 3, 6 and 12, respectively. Basal and peak LH and follicle-stimulating hormone levels were substantially suppressed at months 3, 6 and 12, and most participants showed sex hormone suppression. At months 6 and 12 respectively 92.9% and 89.3% of girls had stable breast development, and all boys had stable genital development. There was a decrease in mean growth velocity from baseline (8.96cm/year) to months 3, 6 and 12 (8.07, 5.24 and 6.94cm/year, respectively). The mean difference between bone and chronological age decreased from baseline (2.85years) to month 12 (2.39years). In girls, uterine length was stable or reduced at month 12; in boys, testicular volume was reduced. Triptorelin was well tolerated. The triptorelin 3-month PR formulation demonstrated similar efficacy to that previously reported in non-Chinese patients with CPP and had an acceptable safety profile. This supports triptorelin 3-month PR as a viable option for Chinese children with CPP.

Eosinophilic Dermatitis due to Triptorelin Pamoate in a Patient with Prostate Cancer Confirmed by Patch Testing.

Eosinophilic Dermatitis due to Triptorelin Pamoate in a Patient with Prostate Cancer Confirmed by Patch Testing.

LCZ696 (sacubitril/valsartan) mitigates cyclophosphamide-induced premature ovarian failure in rats; the role of TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway

AimCyclophosphamide (CP) is used to treat a variety of cancers and autoimmune illnesses. CP has been found to frequently cause premature ovarian failure (POF). The study's objective was to assess LCZ696's potential for protection against CP-induced POF in a rat model. Main methodsRats were randomly assigned into seven groups as follows: control, valsartan (VAL), LCZ696, CP, CP + VAL, CP + LCZ696, and CP + triptorelin (TRI). Ovarian malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-18 (IL-18), IL-1β, and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. Serum anti-mullerian hormone (AMH), estrogen, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also measured using ELISA. The expression of NLRP3/Caspase-1/GSDMD C-NT and TLR4/MYD88/NF-B P65 proteins was estimated using western blot assay. The histopathology of the ovaries was also investigated. The estrous cycle, body, and ovarian weights were also monitored. Key findingsCP treatment significantly elevated levels of MDA, IL-18, IL-1β, TNF-α, FSH, LH, and up-regulated TLR4/NF-κB/NLRP3/Caspase-1 proteins, as compared to the control group, however, ovarian follicles count, and levels of GSH, SOD, AMH, and estrogen were reduced with CP administration. All the aforementioned biochemical and histological abnormalities were considerably alleviated by the LCZ696 therapy compared to valsartan alone. SignificanceLCZ696 effectively mitigated CP-induced POF, offering promising protection that could be related to its suppression power on NLRP3-induced pyroptosis and TLR4/NF-B P65 pathway.

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty.

Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables. We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently. The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment. The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected.

Gonadotropin-releasing hormone analog therapies for children with central precocious puberty in the United States.

Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data suggest similar safety and efficacy profiles over the first year of treatment. One- and 3-month intramuscular (IM) leuprolide acetate (LA) have long-term safety and efficacy data and allow for flexible dosing. Six-month IM triptorelin pamoate offers a longer duration of treatment, but without long-term efficacy and outcome data. Six-month subcutaneous (SQ) LA combines a SQ route of injection and long duration of action but lacks long-term efficacy and outcome data. The 12-month SQ histrelin acetate implant avoids injections and offers the longest duration of action, but requires a minor surgical procedure with local or general anesthesia. Factors in treatment selection include route of administration, needle size, injection volume, duration of action, and cost. The current GnRHa landscape provides options with varying benefits and risks, allowing physicians and caregivers to select the most appropriate therapy based on the specific needs and concerns of the child and the caregiver. Agents have different advantages and disadvantages for use, with no one agent displaying superiority.

The protective effect of fenofibrate, triptorelin, and their combination against premature ovarian failure in rats.

Cyclophosphamide (CP) is a chemotherapy alkylating agent that causes a lot of side effects including premature ovarian failure (POF). This study aimed to evaluate the possible protective effect of fenofibrate (FEN) in CP-induced POF. Rats were randomly divided into five groups as follows: negative control, CP, triptorelin (TRI)-treated, FEN (FEN)-treated, and FEN + TRI-treated. Histological study, collagen area fraction, and immunoexpression of proliferating cell nuclear antigen (PCNA) were evaluated. Also, estrogen, anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and ovarian malondialdehyde (MDA), nitric oxide (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were measured. CP significantly reduced ovarian follicle count, as compared with the control group (1.00 ± 0.76 versus 7.75 ± 1.83, respectively). Meanwhile, FEN, either solely or in combination with TRI, significantly increased ovarian follicle count, as compared with the CP group (3.88 ± 0.83 and 5.75 ± 1.39, respectively). As compared with the control group, CP increased the levels of MDA, NOx, IL-10, TNF-α, FSH, LH, and collagen area fraction; however, levels of GSH, SOD, VEGF, AMH, estrogen, and PCNA immunoexpression were reduced with CP. Administration of FEN either solely or in combination with TRI showed significant improvement in all the parameters previously mentioned. FEN can protect the ovary from CP-induced side effects possibly through antioxidant and anti-inflammatory actions.

SUN-063 Usefulness of a LHRH Test with Low Dose of Triptorelin Pamoate in the Diagnosis of Precocious Puberty in Girls

Objective: to determine diagnosis value of a new LHRH test for diagnosis or precocious puberty (PP) correlated with clinical and paraclinical pubertal changes. Methods:79 girls under age 10 years old were referred to our laboratory with diagnosis of precocious puberty went thought a physical exam and bone age /pelvic US review to classify them clinically in probably PP or unlikely PP. A LHRH test was performed with measurement of at least 3 times including baseline measurement of gonadotrophins (LH / FSH) and estradiol 0-24 hours after a dose of 100 mcg/m2 (max 100 mcg) of Triptorelin Pamoate. The results for LH greater than 8 uUI / L and estradiol of 80 pg / ml were considered positive - Results: From 79 girls, mean age 8,02 years old (+/- 2,2) 41 were classified as likely PP (group 1) and 38 unikely PP (group 2) On group 1, 39 patients (95,1 %) had results of LH above 8 uUI/L. In this group, 5 patients (12.1%) had estradiol results below 80 pg / ml. Of the positive test, 3 patients (7,6%) %) had LH peak time 60 min, 4 patients (10,2%) had LH peak time 90 min, 31 (79,4%) had LH peak at time 180 minutes. In group 2, 3 patients (7,89 %) had values of estradiol above 80 pg/ml and 1 patient had values above 8 uUI/ml. Sensitivity was 95,1% specificity 97,4%, predicted positive value 97,5% and negative predicted value 95%. Conclusion: Low dose LHRH test for precocious puberty with 100 mcg/m2 of Pamoate Triptorelin is a useful tool in the diagnosis of precocious puberty in girls, with high sensitivity and specificity and with lower cost than other diagnostic tools.

Effects of fixed-time artificial insemination using triptorelin on the reproductive performance of pigs: a meta-analysis

Triptorelin (TRI), a gonadotropin-releasing hormone agonist allowing ovulation synchronization in pigs, is indispensable for fixed-time artificial insemination (FTAI) protocols. However, the effect of FTAI using TRI (FTAI-TRI) on the reproductive performance is controversial. We performed a meta-analysis to determine whether FTAI-TRI affects reproductive performance of pigs, including pregnancy rate (PR), number of pigs born alive per litter (NBA), farrowing rate (FR) and total number of pigs born per litter (TNB). A total of 37 trials from 15 studies were extracted and analysed in Stata. A weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for NBA and TNB, and risk ratio (RR) with 95% CI was calculated for PR and FR. Pregnancy rate, TNB and NBA data were applied to a fixed-effect protocol, and FR data were applied to a random-effect protocol. We found that for weaned sows, the FTAI-TRI group had comparable reproductive performance to the artificial insemination (AI) following oestrus detection (EDAI) group. Fixed-time AI has many advantages, including the elimination of the need to heat-check twice daily, so that FTAI-TRI is a good substitute for EDAI. Subgroup analysis indicated that the optimal timing of triptorelin treatment was 96 h after weaning, which gave significant positive effects on PR (RR = 1.08, P = 0.000) and non-significant positive effects on TNB (WMD = 0.12, P = 0.452). Triptorelin at a dose of 100 μg showed better effects than 200 μg, with significant positive effects on PR (RR = 1.09, P = 0.005) and FR (RR = 1.06, P = 0.036). So a single dose of 100 μg was recommended. The optimal protocol was insemination at 24 h and again at 48 h after triptorelin administration if they remained in standing oestrus, and this provided a significantly higher NBA (WMD = 0.59, P = 0.013) that increased by 0.59. For gilts, the FTAI-TRI group showed decreased (not significant) PR (RR = 0.96, P = 0.127) and significantly decreased FR (RR = 0.93, P = 0.013), TNB (WMD = −0.85, P = 0.006) and NBA (WMD = −0.98, P = 0.000), which were inferior to those in the EDAI group. In conclusion, the effects of FTAI-TRI on the reproductive performance of pigs were parity-, treatment timing-, insemination timing-, and dosage-dependent. Fixed-time AI using triptorelin could effectively replace the EDAI protocol for sows, but not for gilts.

Comparison of triptorelin acetate vs triptorelin pamoate in the treatment of Central precocious puberty (CPP): a retrospective study

The aim of this study is to compare the clinical and biochemical outcomes of triptorelin acetate (TPA) versus triptorelin pamoate (TPP) treatment in girls with central precocious puberty. A total of 60 patients with idiopathic CPP were retrospectively recruited. Thirty girls were treated with triptorelin acetate 3.75 mg/month (TPA group) and thirty girls in a second group received triptorelin pamoate 3.75 mg/4 weeks (TPP group). Patient follow-up at 12 and 24 months included GnRH Test at 12 months and baseline LH at 24 months. Patients were monitored with pelvic ultrasound, X-Ray of the hand and wrist and anthropometric evaluations. A total of 60/60 girls showed a good response to both formulations. Significant reductions in basal and LH peaks, estradiol values, breast pubertal stage, progression of bone age and growth velocity rate after 12 months treatment were obtained in both groups, demonstrating the equivalence of the two formulations in regulating the hypothalamic–pituitary-gonadal (HPG) axis. Triptorelin pamoate provided a more effective and significant reduction in LH peak after 12 months in comparison with triptorelin acetate more effective in reducing ovarian volume and endometrial thickness. Both formulations were equivalent, even though the LH peak was significantly lower in girls treated with triptorelin pamoate

Protective mechanisms of triptorelin against tripterygium glycoside-induced ovarian dysfunction

The aim of this study was to investigate the protective effects of Triptorelin (TRI) on Tripterygium Glycoside-induced Ovarian Dysfunction (TG-OD). Thirty mice with normal estrous cycles were randomly divided into three groups (n=10): the control group (group A) was orally administered 0.35 ml of saline daily; the TH group (group B) was orally administered 0.35 ml of TG solution from the 8th d for 10 w continuously; the TG+TRI group (group C) was subcutaneously injected with 0.1 mg/kg TRI daily, as well as orally administered 0.35 ml of TG solution from the 8th d for 10 w continuously. All mice were sacrificed during the 11th week to detect blood anti-Mullerian hormone, follicle-stimulating hormone, luteinizing hormone, and estradiol; calculate the ovarian index; and observe the morphologies of ovarian tissues. Mice in group C were more flexible, and had increased weight, reduced folliclestimulating hormone and luteinizing hormone, and increased anti-Mullerian hormone and estradiol; additionally, ovarian follicles and mature follicles increased. TG caused gonad and ovarian dysfunction in female mice; TRI exhibited protective effects against TG-induced gonad and ovarian dysfunction in female mice.

A 6-Month Trial of the Efficacy and Safety of Triptorelin Pamoate (11.25 mg) Every 3 Months in Children with Precocious Puberty: A Retrospective Comparison with Triptorelin Acetate

Background/Aims: To evaluate the efficacy and safety of a triptorelin pamoate (11.25 mg) 3-month formulation in the management of central precocious puberty (CPP) (TP Study) and to retrospectively compare it with a triptorelin acetate (11.25 mg) 3-month formulation (TA Study). Methods: We conducted two phase III, multicentre, single-stage, non-comparative, open-label studies. In the TP Study, patients with CPP received an intramuscular injection of triptorelin pamoate 11.25 mg at baseline and 3 months after baseline. Hormonal changes as well as safety and efficacy endpoints were measured at baseline, 3 months, and 6 months. Results: The baseline characteristics of the 37 patients in the TP Study were similar to those of the TA Study population. A suppressed luteinising hormone (LH) response (LH peak ≤3 IU/l) to the gonadotrophin-releasing hormone test at 3 months (primary endpoint) occurred in 83.8 and 82.8% of the cases in the TP and the TA Study, respectively. At 6 months, a suppressed LH response occurred in 86.5 and 96.8% of the cases in the TP and the TA Study, respectively. Pubertal development was slowed in both studies. Adverse events were mild to moderate and resolved without sequelae in the TP Study. Conclusion: Triptorelin pamoate 11.25 mg administered at 3-month intervals is an effective and well-tolerated treatment in patients with CPP. The efficacy and safety profiles appear similar to those reported in the literature for triptorelin acetate 11.25 mg.

Triptorelin and cetrorelix induce immune responses and affect uterine development and expressions of genes and proteins of ESR1, LHR, and FSHR of mice

Context: GnRH immunity can reduce the expression of pituitary GnRH levels, and cause the changes in reproductive behaviors. It is unclear whether triptorelin (TRI) and cetrorelix (CET) immunity influences uterine development and expression of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and estradiol receptor 1 (ERS1) in the uterus.Objective: The study investigated the effects of active immunity of GnRH agonist and antagonist on uterine development, microstructures, expression of hormone receptors mRNAs, and proteins in uteri.Materials and methods: One hundred and five mice were assigned into CET, TRI, and control groups (CG). Mice in CET-1, CET-2, and CET-3 (n = 15) were subcutaneously injected with 10, 20, and 40 μg CET antigens for seven days, respectively. Mice in TRI-1, TRI-2, and TRI-3 were injected with 10, 20, and 40 μg TRI antigens for seven days, respectively. The qPCR and Western blot were implemented to determine expressions of ESR1, LHR and FSHR mRNAs, and proteins.Results: Compared with CG, the uterine weights of CET-1, CET-2, and CET-3 increased by 42.86, 62.86, and 10.00% on day 35 (p < 0.05), respectively. Uterine weights of TRI-2, TRI-3 reduced by 28.57% and 11.43% (p < 0.05), respectively. The uterine cavity in CET-1, CET-2, and CET-3 increased; the uterine wall became thick. The cytoplasm of endometrial epithelial cells (EEC) increased slightly. In TRI group, the uterine wall thinned. Uterine cavity became narrow slightly in TRI-1. Numbers of uterine glands reduced. The endometrium epithelial thickness (EET) in CET-1 and CET-2 increased by 68.21% and 79.46% (p < 0.05), respectively. EET in TRI-1 was decreased by 13.69%. Uterine wall thicknesses (UWT) in CET-1 and CET-2 were higher than CG, with the increment of 28.59% and 30.72%. UWT of TRI-1, TRI-2, and TRI-3 reduced by 29.35, 15.36, and 14.41%, respectively. Expressions of ESR1, FSHR, and LHR mRNAs in CET and TRI mice increased. ESR1 and FSHR protein levels increased in all experimental mice (p < 0.05), with a maximum of TRI-3. LHR protein levels of the CET decreased. LHR protein levels of TRI group increased, with a maximum of TRI-3 (p < 0.05). ESR1 protein level had significant negative correlations to mRNA expressions of ESR1, LHR, and FSHR.Conclusions: CET immunity promoted the uterine development, improved EET and UWT, and also promoted the expressions of ESR1 and FSHR protein levels. It lessened the LHR protein levels. TRI immunity blocked EET and UWT, inhibited uterine growth and development. The efficacy of CET immunity was more obvious than TRI.

Cetrorelix and Triptorelin active immunization influences follicle development and receptor expressions of ovaries in mice

The study investigated comparatively the effects of active immunization of Cetrorelix and Triptorelin on the follicle development, histological structures, and expressions of FSHR and LHR proteins in the ovary. One hundred and five female mice, 35 days old, and body weight of 26.56±2.89g, were randomly assigned into Cetrorelix (CET), Triptorelin (TRI) and control groups (CG). Mice in CET-1, CET-2 and CET-3 (n=15) were subcutaneously injected with 0.1, 0.2 and 0.4mL Cetrorelix antigen (100μg/mL) for seven days, respectively. Mice in TRI-1, TRI-2 and TRI-3 were injected with 0.1, 0.2 and 0.4mL Triptorelin antigen (100μg/mL) for seven days. Mice in CG (n=15) were injected with 0.2mL saline for seven days. Western blotting was utilized to determine the expressions of follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) proteins. ELISA was used to measure the serum FSH and LH concentrations. The ovarian slices were observed under optical microscopy. The results showed that the ovarian weights of CET and TRI groups increased slightly with a maximum increment of 27.02% of CET-1 mice on day 35. Ovarian weights in TRI group increased dose-dependently with a maximum increment of 45.77% in TRI-3 on day 35. The numbers of the primordial follicle (POF), primary follicle (PF), secondary follicle (SF) and mature follicle (MF) of CET and TRI groups increased at different degrees when compared to CG. The granular layer in SF was arranged tightly and zona pellucida (ZP) was thickened. Follicles developed fully. Follicle longitudinal diameter (FLD), follicle transverse diameter (FTD) and follicle wall thickness (FWT) in CET and TRI groups increased as compared to CG. FLD, FTD and FWT of TRI-3 had a larger increment than CG and CET-1 on days 21 and 35. Expression levels of FSHR and LHR proteins in TRI group increased when compared to CG. Expression levels of FSHR and LHR proteins of CET group decreased. Serum FSH of TRI group was slightly higher than the CG and CET group on day 21. On day 35, serum FSH levels of CET-1 and TRI-1 were greater than CG and the rest of the subgroups. Serum FSH levels had no significant differences among all groups. Expression levels of LHR and FSHR proteins in CET group had obvious negative correlations to FLD, FTD and FWT. However, in the TRI group, these correlations were positive. In conclusion, Cetrorelix and Triptorelin immunization could improve ovarian growth, increase the follicle numbers, enhance dose-dependently the FLD, FTD and FWT, and eventually promote the ovary and follicle development. Cetrorelix decreased expression levels of FSHR and LHR proteins in the ovaries of mice. Triptorelin enhanced expression levels of FSHR and LHR proteins. Triptorelin treatment had more obvious effects than Cetrorelix treatment.

Efficacy of triptorelin pamoate 11.25 mg administered subcutaneously for achieving medical castration levels of testosterone in patients with locally advanced or metastatic prostate cancer

Gonadotropin-releasing hormone agonists are widely used as androgen deprivation therapy in many men with locally advanced or metastatic prostate cancer. Gonadotropin-releasing hormone agonists are delivered by intramuscular injection every 1, 3 or 6 months, but in some patients subcutaneous injection may be more appropriate. This study assessed the efficacy and safety profile of the gonadotropin-releasing hormone agonist, triptorelin pamoate, when administered by the subcutaneous route. In this multicentre, open-label, single-arm study, androgen deprivation therapy-naïve men with locally advanced or metastatic prostate cancer received the gonadotropin-releasing hormone agonist triptorelin pamoate 11.25 mg (3-month formulation) by the subcutaneous route twice (at baseline and 13 weeks later). The co-primary efficacy endpoints were the proportion of patients with a castration level of serum testosterone (<50 ng/dl) after 4 weeks, and of these, those still castrated after 26 weeks. Of the 126 treated patients, 123 [97.6%; 95% confidence interval (CI): 93.2-99.5)] were castrated 4 weeks after the first subcutaneous injection, and 115/119 patients (96.6%; 95% CI: 91.6-99.1) castrated at 4 weeks maintained castration at 26 weeks. Median prostate-specific antigen levels were reduced by 64.2 and 96.0% at 4 and 26 weeks, respectively. The probability of maintaining a testosterone level <20 ng/dl up to 26 weeks was 90.0% (95% CI: 85.0-95.0). The most frequently occurring treatment-related adverse events were typical of gonadotropin-releasing hormone agonist treatment (hot flushes, increased weight, erectile dysfunction and hyperhidrosis). This study demonstrates that triptorelin pamoate 11.25 mg administered by the subcutaneous route every 3 months is as efficacious and well tolerated as administration via the intramuscular route in men with locally advanced or metastatic prostate cancer.

Health-related quality of life in patients with advanced prostate cancer undergoing treatment with TRIPTOrelin Pamoate SIX month formulation: Results of the non-interventional TRIPTOSIX study.

287 Background: Preserving quality of life (QoL) is an important therapeutic aim in advanced prostate cancer (PCa). The effects of treatment on QoL were studied in a non-interventional study performed from 2010 until 2012 evaluating 1 year of treatment with a LHRH agonist, triptorelin pamoate 6-month depot (TP 6M). Methods: Data of 564 patients with advanced PCa treates in 129 German urology outpatient clinics were analysed. Data on QoL were collected by EORTC questionnaires (QLQ-C30 and -PR25) at baseline, 6 months and 12 months. The QLQ-C30 assesses functional QoL, global health and symptoms of disease, the QLQ-PR25 covers PCa specific symptoms and sexual activity. A clinically relevant improvement, i.e. increase of ≥10 points in the QLQ-C30 global health status/QoL scale, defined treatment responders. Response at month 6 compared to baseline was the primary study endpoint. Results: GlobalHealth Related (HR) QoL was similar over the 1 year follow-up period with a mean (± SD) score of 60.9 (±21.8) at baseline and 61.7 (±22.2) at 12 months. Within the first 6 months, 24.0% of patients were identified as responders (i.e. a clinically relevant improvement in this parameter of ≥10 points). The responder rate was maintained at 12 months of treatment (25.5%). This trend in QoL was also seen in the QLQ-C30 subscales, which were generally similar over the study period. QLQ-PR25 scores were also found to be similar over 1 year, although some deterioration was reported by sexually active patients, as expected. Subgroup analyses on response rates identified age, risk group, pretreatment for PCa and baseline QoL scores as predictors of change in QoL. Conclusions: Treatment with TP 6M over 12 months is associated with few changes in HRQoL and might lead in some patients to clinically meaningful improvements of HRQoL.