Triptorelin

Objective: To evaluate the efficacy and safety of triptorelin acetate microspheres for injection compared with triptorelin acetate for injection in the treatment of endometriosis. Methods: A total of 392 patients with endometriosis were prospectively enrolled from 47 research centers across China between October 25, 2021, and February 14, 2023. Participants were randomly assigned in a 1∶1 ratio to either the experimental group (n=196) or the control group (n=196). Both groups received intramuscular injections of the respective drugs once every 4 weeks for a total of 6 doses. The primary efficacy endpoint was the percentage of subjects with suppressed estradiol levels after treatment. Secondary endpoints included pain relief, amenorrhea rate, changes in ovarian endometrioma diameter, and adverse drug reactions. Results: For the primary efficacy endpoint, the percentages of subjects with suppressed estradiol levels at week 12 in the experimental and control groups were 97.3% (177/182) and 98.4% (181/184), respectively. The rate difference was -1.1% (95%CI: -4.8% to 2.3%), the lower limit of the 95%CI for the rate difference was greater than the non-inferiority margin of -10%. Compared to baseline, visual analog scale (VAS) scores for dysmenorrhea and non-menstrual pelvic pain decreased at all post-treatment time points in both groups, with no statistically significant differences between two groups (all P>0.05). Estradiol, luteinizing hormone, and follicle stimulating hormone levels significantly decreased from baseline at all post-treatment time points in both groups (all P<0.05), with no significant intergroup differences (all P>0.05). No significant differences were observed in amenorrhea rates between two groups at week 8, 12, and 24 post-treatment (all P>0.05). However, the time to menstruation recovery after drug discontinuation was significantly earlier in the experimental group than that in the control group (P=0.003). Carbohydrate antigen 125 levels significantly decreased from baseline at week 12 and 24 post-treatment in both groups (all P<0.001), but no significant intergroup differences were found (all P>0.05). In the experimental group, only the diameter of the right ovarian endometrioma showed a significant decrease from baseline at week 24 post-treatment (P=0.016). In the control group, neither left nor right ovarian endometrioma diameters showed significant changes from baseline (all P>0.05). The overall incidence of adverse drug reactions was similar between the experimental and control groups [77.6% (152/196) vs 78.6% (154/196), respectively; P>0.05]. Conclusions: Triptorelin acetate microspheres for injection is an effective treatment for endometriosis. It could maintain low estrogen levels, consistently alleviate endometriosis-associated pain, achieve a high rate of amenorrhea during treatment, and reduce the size of ovarian endometrioma to some extent, demonstrating a favorable safety profile.

AIM: To evaluate the efficacy and safety of triptorelin after radical prostatectomy (RP) in patients with negative lymph nodes. METHODS: PRIORITI (NCT01753297) was a prospective, open-label, randomized, controlled, phase 4 study conducted in China and Russia. Patients with high-risk (Gleason score ≥ 8 and/or pre-RP prostate-specific antigen [PSA] ≥ 20 ng/mL and/or primary tumor stage 3a) prostate adenocarcinoma without evidence of lymph node or distant metastases were randomized to receive triptorelin 11.25 mg at baseline (≤ 8 weeks after RP) and at 3 and 6 months, or active surveillance. The primary endpoint was biochemical relapse-free survival (BRFS), defined as the time from randomization to biochemical relapse (BR; increased PSA > 0.2 ng/mL). Patients were monitored every 3 months for at least 36 months; the study ended when 61 BRs were observed. RESULTS: The intention-to-treat population comprised 226 patients (mean [standard deviation] age, 65.3 [6.4] years), of whom 109 and 117 were randomized to triptorelin or surveillance, respectively. The median BRFS was not reached. The 25th percentile time to BRFS (95% confidence interval) was 39.1 (29.9-not estimated) months with triptorelin and 30.0 (18.6-42.1) months with surveillance (p = 0.16). There was evidence of a lower risk of BR with triptorelin versus surveillance but this was not statistically significant at the 5% level (p = 0.10). Chemical castration was maintained at month 9 in 93.9% of patients who had received triptorelin. Overall, triptorelin was well tolerated and had an acceptable safety profile. CONCLUSION: BRFS was observed to be longer with triptorelin than surveillance, but the difference was not statistically significant. PLAIN LANGUAGE SUMMARY: After a diagnosis of prostate cancer, one of the current treatments is surgical removal of the prostate and its cancer from the body. This is called radical prostatectomy. This may cure the person. Unfortunately, sometimes the tumor may have already spread into neighboring cells (lymph nodes). If this has happened, we know that giving people a chemical castration therapy to lower their levels of male sex hormones may reduce the risk of the cancer spreading further. This is achieved by giving people an androgen deprivation therapy (ADT), such as triptorelin (which is used in this study). What we do not yet know, and what we investigated in this study, is whether ADT can also benefit people who do not have signs that their cancer has already spread to the lymph nodes. Our study involved 226 men from China and Russia and investigated whether giving triptorelin for 9 months would lead to better outcomes compared with giving no additional treatment (active surveillance). All people in the study had radical prostatectomy but only half of them were given triptorelin in the following 8 weeks. The time frame of 8 weeks was used because this is the time needed to make sure that the surgery had gone well, and that no biological markers of cancer were still present in the person's blood (the marker is called prostate-specific antigen [PSA]). High levels of PSA are a sign that the prostate cancer has returned. People were monitored for 3 years with regular checks of their castration status and levels of the cancer marker (PSA). At the end of the study, we saw that it took longer for PSA levels to increase for people who had taken triptorelin than it did for those who had not had additional treatment, but the difference was not statistically significant. There were no unexpected safety concerns seen among the people taking triptorelin. Our findings are promising but more studies are needed to confirm if starting triptorelin shortly after surgery can benefit this group of people who have had their prostate cancer treated by radical prostatectomy and have no signs that their cancer has spread to the lymph nodes. [Correction added on 31th July 2024, after first online publication: Plain language summary is added in this version.].

This study evaluates clinical efficacy of cluster nursing plus triptorelin in pediatric precocious puberty and its impact on patient quality of life. A total of 110 children with precocious puberty hospitalized between June 2022 and June 2024 were enrolled. To ensure comparability, participants were grouped using propensity score matching based on the nursing method previously received, along with sex, age, and baseline characteristics. The subjects were then randomized into 2 groups: the control group (n = 55), which received standard therapy, and the study group (n = 55), which received cluster nursing plus triptorelin treatment in addition to the standard care regimen. The clinical efficacy, growth and development indicators, children's behavioral problems, quality of life, and the occurrence of adverse reactions were observed and compared between the 2 groups. The total effective rate after intervention was significantly higher in the study group (96.36%) than in the control group (85.45%) (P < .05). After intervention, bone age and predicted adult lifetime high level were increased in both groups compared with before intervention, luteinizing hormone and T were decreased compared with before intervention, the study group demonstrated significantly higher predicted adult height versus controls, while bone age, luteinizing hormone, and T levels were significantly lower versus controls (P < .05). Post-intervention depression scores, social withdrawal, hyperactivity and aggression in both groups were lower than before intervention, and the scores of depression, social withdrawal, hyperactivity, and aggression in the study group were lower than those in the control group (P < .05). After intervention, scores of family life, peer interaction, school life, living environment, self-knowledge, physical emotion, living environment, anxiety experience, and depression experience in both groups were higher than before intervention, and scores of family life, peer interaction, school life, living environment, self-knowledge, physical emotion, anxiety, and depression scores significantly exceeded control group levels in the study group (P < .05). Post-intervention adverse reaction incidence was 3.64% lower in the study group versus controls (10.91%) (P < .05). The combination of cluster nursing and triptorelin therapy can effectively control the growth and development of children with precocious puberty, improve their behavior problems and quality of life. It has high safety and effectiveness and is worthy of popularization and application.

INTRODUCTION: This phase 3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP). METHODS: In this open-label study (NCT05029622), Chinese children (girls < 9 years, boys < 10 years) received two doses of triptorelin pamoate 22.5 mg (day 1 and month 6). Primary endpoint was the proportion at month 6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5 IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline. RESULTS: Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5-9] years). At month 6, all patients had LH suppression; this was maintained at month 12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months 3 to 12 had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month 6 and 12, respectively; all boys had regression or stable genital development until month 12. Compared with baseline (9.82 cm/year), mean growth velocity was 5.88 cm/year at month 6 and 5.17 cm/year at month 12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month 6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month 6 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. CONCLUSION: 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: Trial registration: ClinicalTrials.gov identifier, NCT05029622.

CONTEXT: Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic ovary syndrome (PCOS) compared with healthy women or those with hypothalamic amenorrhea (HA). OBJECTIVE: We compared the gonadotropin response to triptorelin in healthy women, women with PCOS, or those with HA without ovarian stimulation, and in women with or without polycystic ovaries undergoing oocyte donation cycles after ovarian stimulation. METHODS: The change in serum gonadotropin levels was determined in (1) a prospective single-blinded placebo-controlled study to determine the endocrine profile of triptorelin (0.2 mg) or saline-placebo in healthy women, women with PCOS, and those with HA, without ovarian stimulation; and (2) a retrospective analysis from a dose-finding randomized controlled trial of triptorelin (0.2-0.4 mg) in oocyte donation cycles after ovarian stimulation. RESULTS: In Study 1, triptorelin induced an increase in serum luteinizing hormone (LH) of similar amplitude in all women (mean peak LH: healthy, 52.3; PCOS, 46.2; HA, 41.3 IU/L). The AUC of change in serum follicle-stimulating hormone (FSH) was attenuated in women with PCOS compared with healthy women and women with HA (median AUC of change in serum FSH: PCOS, 127.2; healthy, 253.8; HA, 326.7 IU.h/L; P = 0.0005). In Study 2, FSH levels 4 hours after triptorelin were reduced in women with at least one polycystic morphology ovary (n = 60) vs normal morphology ovaries (n = 91) (34.0 vs 42.3 IU/L; P = 0.0003). Serum anti-Müllerian hormone (AMH) was negatively associated with the increase in FSH after triptorelin, both with and without ovarian stimulation. CONCLUSION: FSH response to triptorelin was attenuated in women with polycystic ovaries, both with and without ovarian stimulation, and was negatively related to AMH levels.

OBJECTIVE: Long-acting triptorelin (LAT) (22.5 mg) is a gonadotropin-releasing hormone (GnRH) agonist used in men with prostate cancer. This study investigated the prescription pattern of LAT in a real-world setting and its efficacy. PATIENTS & METHODS: This was a retrospective review of patients in a tertiary center who were prescribed LAT for prostate cancer from January 2018 to March 2023 after the introduction of LAT in the territory. Demographic data were collected, and LAT prescription patterns were reviewed. These patterns included the indication and duration of prescription, testosterone suppression and characteristics of the primary prostate cancer. RESULTS: A total of 237 prostate cancer patients were prescribed LAT in the study period. The indications for LAT included metastatic prostate cancer (50.6%), neoadjuvant/adjuvant therapy for radiotherapy (28.7%) and neoadjuvant therapy for radical prostatectomy (5.1%). Among the cohort, 41.4% of the patients were receiving short-acting triptorelin (11.25 mg) before LAT initiation, 15.2% were receiving other GnRH agonists, and 15.6% were receiving GnRH antagonists. The median age at the first dose of LAT and the median treatment duration were 72 (53-94) years and 30 (6-72) months, respectively. During the study period, 92.0% of the patients did not receive another form of hormonal treatment other than LAT. A total of 121 (51.1%) patients had their testosterone level checked after LAT initiation. The median time interval of testosterone measurement after LAT initiation was 8 (1-47) months, with 98.3% of the patients having a testosterone level < 1.7 nmol/L and 92.6% having a level < 0.7 nmol/L. Among the cohort, 1 patient stopped LAT due to hot flashes and muscle weakness. CONCLUSION: The LAT adherence rate was high in the setting of hormonal treatment for prostate cancer. Testosterone suppression was satisfactory after the initiation of LAT and was generally well tolerated.