Gonadotropin?releasing hormone agonists in prostate cancer: A comparative review of efficacy and safety

Androgen deprivation therapy (ADT) using gonadotropin?releasing hormone agonist (s) (GnRH?A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH?A. All GnRH?A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (?50 ng/dL in a month and ?20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ?50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate?specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10?year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10?year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10?year survival rate of 87%, and triptorelin had an 8?year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH?A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH?A. Goserelin appears to be the most convenient of all the GnRH?A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH?A for ADT in prostate cancer.

Research progress of the efficacy and safety of 3-month depot Leuprorelin in the treatment of central precocious puberty / 中华实用儿科临床杂志

Central precocious puberty (CPP) is a common pediatric endocrine disease caused by premature activation of the hypothalamic-pituitary-gonadal axis, featured by rapid development of internal and external reproductive organs and secondary sexual characteristics in girls before age 8 and boys before age 9.The gonadotropin-releasing hormone analogue (GnRHa) is the first choice for the treatment of CPP.Currently, 3.75 mg/ month sustained -release short-acting dosage form (1M depot formulations) is the most commonly used in China.The development of long-acting dosage form will reduce injection times and clinic visits.At present, the 3-month long-acting dosage form (11.25 mg 3M depot formulations) of Leprorelin microsphere has been approved in China.However, clinical practice experience of 3-month Leuprorelin acetate depot formulations is lacking in China.Therefore, in this paper, existing clinical evidence for this dosage form was reviewed to provide evidence-based medicine support for its clinical application.

Clinical efficacy of leuprorelin combined with mifepristone in the treatment of endometriosis / 中国基层医药

Objective@#To observe the clinical efficacy of leuprorelin combined with mifepristone in the treatment of endometriosis.@*Methods@#From September 2014 to September 2016, 168 cases of endometriosis were selected in the research.The patients were divided into the control group and the research group according to the random number table method, with 84 patients in each group.All patients underwent laparoscopic endometrial debridement with fertility preservation.The control group was treated with mifepristone, while the study group was treated with combination of leuprorelin and mifepristone.The incidence of adverse drug reactions during treatment was observed, the levels of serum E2, LH, FSH, EmAb and CA125 were detected before and after treatment, the curative effect after treatment was evaluated, and the recurrence and pregnancy of endometriosis within 12 months after treatment were followed.@*Results@#During the treatment, the incidence rate of adverse drug reactions in the study group(17/84, 20.24%) had no statistically significant difference compared with the control group (13/84, 15.48%) (χ2=0.649, P=0.420). The levels of serum estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), anti-endometrial antibody (EmAb) and carbohydrate antigen 125 (CA125) in the two groups were significantly lower than those before treatment (t=17.694, 13.271, 7.943, 4.315, 10.029, 7.952, 14.231, 10.610, 27.953, 22.436, all P<0.001), and the indicators in the study group were significantly lower than those in the control group (t=5.217, 3.859, 3.526, 4.337, 6.048, all P<0.001). The total effective rate of the study group (96.43%) was significantly higher than that of the control group (83.33%) (χ2=7.919, P=0.005). Within 12 months after treatment, the recurrence rate of endometriosis in the study group (2.38%) was significantly lower than that of the control group (15.48%), while the rate of pregnancy (48.81%) was significantly higher than that of the control group(27.38%), there were statistically significant differences between the two groups (χ2=8.858, 8.178; P=0.003, 0.004).@*Conclusion@#Compared with leuprorelin treatment alone, leuprorelin combined with mifepristone can significantly reduce the serum levels of E2, LH, FSH, EmAb and CA125 in patients with endometriosis, and improve the overall treatment of endometriosis, reduce recurrence, promote pregnancy, and has high safety.

Clinical efficacy of leuprorelin combined with mifepristone in the treatment of endometriosis / 中国基层医药

To observe the clinical efficacy of leuprorelin combined with mifepristone in the treatment of endometriosis.Methods From September 2014 to September 2016,168 cases of endometriosis were selected in the research.The patients were divided into the control group and the research group according to the random number table method,with 84 patients in each group.All patients underwent laparoscopic endometrial debride-ment with fertility preservation.The control group was treated with mifepristone ,while the study group was treated with combination of leuprorelin and mifepristone.The incidence of adverse drug reactions during treatment was observed , the levels of serum E2,LH,FSH,EmAb and CA125 were detected before and after treatment ,the curative effect after treatment was evaluated,and the recurrence and pregnancy of endometriosis within 12 months after treatment were followed.Results During the treatment,the incidence rate of adverse drug reactions in the study group (17／84, 20.24%) had no statistically significant difference compared with the control group (13／84,15.48%) (χ2 ＝0.649, P＝0.420).The levels of serum estradiol (E2),luteinizing hormone (LH),follicle stimulating hormone (FSH),anti-endometrial antibody (EmAb) and carbohydrate antigen 125 (CA125) in the two groups were significantly lower than those before treatment (t＝17.694,13.271,7.943,4.315,10.029,7.952,14.231,10.610,27.953,22.436,all P＜0.001),and the indicators in the study group were significantly lower than those in the control group (t＝5.217, 3.859,3.526,4.337,6.048,all P＜0.001).The total effective rate of the study group (96.43%) was significantly higher than that of the control group (83.33%) ( χ2 ＝7.919,P＝0.005).Within 12 months after treatment,the recurrence rate of endometriosis in the study group (2.38%) was significantly lower than that of the control group (15.48%), while the rate of pregnancy ( 48.81%) was significantly higher than that of the control group (27.38%),there were statistically significant differences between the two groups (χ2 ＝8.858,8.178;P＝0.003, 0.004).Conclusion Compared with leuprorelin treatment alone , leuprorelin combined with mifepristone can significantly reduce the serum levels of E2,LH,FSH,EmAb and CA125 in patients with endometriosis,and improve the overall treatment of endometriosis ,reduce recurrence,promote pregnancy,and has high safety.

Therapeutic Effects of Leuprorelin (Leuprolide Acetate) in Sexual Offenders with Paraphilia

BACKGROUND: This study examined the clinical effects of leuprolide acetate in sexual offenders with paraphilic disorders evaluated by means of objective psychiatric assessment. METHODS: The subjects of this study were seven sexual offenders who were being treated by means of an injection for sexual impulse control by a court order. They had been diagnosed with paraphilia by a psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and had been put on probation by the Ministry of Justice between January 2016 and December 2016. RESULTS: After twelve months, we observed significant improvement in symptoms, as decrease of abnormal sexual interest and activity, sexual fantasy, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Impulsivity (GCI-I). There were a mild feminization of the body shape, feelings of fatigue, and mild hot flushes. No other adverse effect was reported. CONCLUSION: These results suggested that the clinical effects of leuprolide acetate in sexual offenders might be an effective treatment and safety strategy.

Protective effect of leuprorelin particle application before laparoscopic cystectomy on ovarian reserve function in ovarian endometriosis / 中国生化药物杂志

Objective To study the protective effect of leuprorelin particle on ovarian reserve function applied before the laparoscopic cystectomy of ovarian endometriosis.Methods 106 patients with endometriosis treated from January 2015 to December 2015 in our hospital were selected.The subjects were divided into two groups according to the random number table, 53 cases of each group.The control group adopted the laparoscopic surgery;the observation group took the leuprorelin particle before the laparoscopic surgery.The operation condition, ovarian hormone and function were observed. Results The operation time and bleeding amount in observation group was better than control group ( P <0.05 ) .After surgery, the exhaust time between two groups had no significantly different.After surgery, the level of follicle stimulating hormone (FSH) in observation group was lower than control group; the level of estradiol (E2) in observation group was higher than control group (P <0.05); the level of luteinizing hormone (LH) between two groups had no significantly different.After surgery, the ovarian volume and antral follicle count ( AFC) in observation group was better than control group (P<0.05).Conclusion Before the laparoscopic cystectomy of ovarian endometriosis, the leuprorelin particle protects the ovarian function and morphology and has less impact in the level of hormone.

A Case of Foreign Body Granuloma Caused by Subcutaneous Injection of Leuprorelin Acetate / 대한피부과학회지

Leuprorelin acetate is a synthetic analog of luteinizing hormone-releasing hormone (LHRH). Recently, hormone-dependent tumors (prostate cancer and breast cancer) have been treated without surgery using this LHRH agonist. A 74-year-old man presented with a subcutaneous tumor in the abdomen. He had received a subcutaneous injection of depot leuprorelin acetate 2 months previously and radiotherapy for prostate cancer. The subcutaneous tumor was totally excised. Histopathologic findings revealed necrosis of fat tissue, many granulomatous nodules composed of giant cells with vacuoles in the dermis and subcutis, and inflammatory cell infiltrates, including mainly lymphohistiocytes. A diagnosis of foreign body granuloma due to depot injection of leuprorelin acetate was made. He revisited our hospital after 1 month with a subcutaneous tumor on his Lt. upper arm. He had received a subcutaneous injection of leuprorelin acetate 1 week ago on that site. We treated it with intralesional triamcinolone injection. Here, we report a case of granulomatous reaction due to leuprorelin acetate injection, which produced subcutaneous nodules.

Ovarian suppression with leuprorelin in combination with aromatase inhibitors in treatment of recurrent/metastatic breast cancer in premenopausal patients / 肿瘤

Objective: To evaluate the efficacy of ovarian suppression (leuprorelin) combined with aromatase inhibitor (AI) in treatment of recurrent/metastatic breast cancer in premenopausal patients and the prognosis. Methods: Fifty-one premenopausal patients with recurrent/metastatic breast cancer were treated with hypodermic injection of 3.75 mg leuprorelin every 28 days and daily oral AI. The clinical efficacy and the survival were evaluated. The prognosis-related factors were analyzed. Results: The objective response rate was 21.6 (11/51), and the clinical benefit rate was 72.5% (37/51). The median progression-free survival (PFS) was 15.2 months (95% confidence interval: 6.3-24.2 months). In univariate analysis, the patients whose estrogen receptor (ER) and progesterone receptor (PR) were both positive and the disease-free survival was ≥ 2 years had a better meidan progression-free survival (PFS) than those whose estrogen receptor (ER) or progesterone receptor (PR) was positive (21.3 vs 8.1 months, P = 0.002) and the disease-free survival was < 2 years (21.3 vs 8.1 months, P = 0.005); the patients not treated with salvage chemotherapy had a better median PFS than those who were treated with salvage chemotherapy (21.3 vs 9.2 months, P = 0.026). The multivariate analysis revealed that ER/PR status was an independent factor of PFS. Conclusion: The combination of leuprorelin and AI is an effective and safety endocrine therapy for premenopausal patients with recurrent/metastatic breast cancer, and it is recommended as a first-line therapy for hormone-dependent recurrent/metastatic breast cancer in premenopausal patients.

A Case of Mental Retardation with Paraphilia Treated with Depot Leuprorelin

Paraphilia is a psychiatric disease that has been difficult to cure. However, recently developed therapeutic methods hold promise. The patient was a 20-yr-old male with chief complaints of continuous masturbation, genital exposure, and aggressive behavior that started 2 yr ago. We administered leuprorelin 3.6 mg intramuscular injection per month, a depot gonadotrophin-releasing hormone analogue, to this patient who a severe mentally retardation with paraphilia. The clinical global impression (CGI)-severity, CGI-improvement and aberrant behavior checklist were performed. After one month, we observed significant improvement in symptoms, such as decreases of abnormal sexual behavior and sexual desire. The GnRH analogues are suggested to be used as an alternative or supplementary therapeutic method for sexual offenders after clinical studies.

Incidence Rate of Injection-Site Granulomas Resulting from the Administration of Luteinizing Hormone-Releasing Hormone Analogues for the Treatment of Prostatic Cancer

PURPOSE: Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas. MATERIALS AND METHODS: We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate. RESULTS: Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate. CONCLUSION: The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.

Inhibitory effect of domestic leuprorelin acetate microspheres on experimentally induced endometriosis in rats / 中国临床药理学与治疗学

Aim To study the effect of leuprorelin acetate microspheres (LE ms) on endometriosis in rats, and compare the efficacy of material drug (LE), domestic and imported LE ms (enanton). Methods Endometriosis was induced by endometrial implant in rats. Then the animals were treated with LE (20 ?g?kg -1 ?d -1 ? 28 d ,sc), enanton(20 ?g?kg -1 ?d -1 ,sc)and domestic LE ms ( 2,20,200 ?g?kg -1 ?d -1 ,sc). Results Implants in control group continued to grow, while those in groups treated with drugs shrinked significantly, and domestic LE ms could produce dose dependent inhibitory effect on the growth of endometrial implant in rats. Conclusion The domestic LE ms at the single dose of 20 ?g?kg -1 ?d -1 has the same effectiveness as enanton and routine injection with the same does of LE for 28 days.