Objective： We aimed to evaluate the efficiency of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly （3.75 mg） depot formul...Objective： We aimed to evaluate the efficiency of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres for patients with metastatic prostate cancer. Methods： A total of 23 patients with metastatic prostate cancer were enrolled in the prospective study and received 6 monthly intramuscular depot injections of domestic substitute of leuprorelin acetate microspheres. Their levels and patterns of serum testosterone suppression and the potential for agonistic stimulation of serum testosterone were monitored following injection monthly （3.75 rag） depot formulation of domestic substitute of leuprorelin acetate microspheres for 24 weeks. Results： Mean testosterone was 431.4 ng/dL, 119.3 ng/dL, 28.2 ng/dL by week 1, 2, 3 and decreased to less than 15.6 ng/dL by week 4 where it remained throughout the treatment period. Median time to suppression of serum testosterone was 20.7 days. No transient minor ＂escape＂ from suppression occurred in all patients which was defined as a single testosterone value greater than 50 ng/dL once suppression was achieved. Assessment of agonistic stimulation following the second depot injection revealed no pattern of stimulation. Conclusion： We concluded that monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres could provide persistent, stable suppression of serum testosterone throughout the dosing intervals, and that the initial depot injection of this formulation also could provide sufficient pituitary desensitization to prevent agnostic stimulation of serum testosterone during chronic treatment.展开更多
Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during ...Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin®conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.展开更多
Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in...Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.展开更多
目的观察滋阴泻火方联合亮丙瑞林治疗女童特发性中枢性性早熟(Idiopathic central precocious puberty,ICPP)的临床疗效。方法选取2022年6月—2023年6月河北中医药大学第一附属医院收治的82例ICPP女患儿,采用随机数字表法分为对照组和...目的观察滋阴泻火方联合亮丙瑞林治疗女童特发性中枢性性早熟(Idiopathic central precocious puberty,ICPP)的临床疗效。方法选取2022年6月—2023年6月河北中医药大学第一附属医院收治的82例ICPP女患儿,采用随机数字表法分为对照组和观察组,每组各41例。对照组给予亮丙瑞林常规治疗,观察组在对照组基础上加用滋阴泻火方口服,两组患儿均连续治疗24周。观察比较两组患儿临床疗效,治疗前后中医证候积分,乳房发育情况,血清激素水平[黄体生成素(Luteinizing hormone,LH)、雌激素(Estrogen,E_(2))、促卵泡成熟素(Follicle stimulating hormone,FSH)],卵巢容积、子宫容积及卵泡直径,BA/CA及预测终身高。结果治疗后两组患儿中医证候积分均较治疗前明显降低,差异有统计学意义(P<0.01);且观察组中医证候积分明显低于对照组,差异有统计学意义(t=4.48、4.36、4.29,P<0.05)。治疗后观察组TannerⅡ期与Ⅲ期总占比明显低于对照组,差异有统计学意义(Z=8.25,P<0.01)。治疗后两组患儿E_(2)、LH及FSH水平均较治疗前明显降低,差异有统计学意义(P<0.05);且观察组E_(2)、LH及FSH水平均明显低于对照组,差异有统计学意义(t=5.86、7.49、5.43,P<0.05)。治疗后两组患儿卵巢容积、子宫容积及卵泡直径均较治疗前明显降低,差异有统计学意义(P<0.05);且观察组患儿卵巢容积、子宫容积及卵泡直径均明显低于对照组,差异有统计学意义(t=4.36、4.41、5.25,P<0.05)。治疗后两组患儿BA/CA均较治疗前明显降低,预测终身高均较治疗前明显升高,差异有统计学意义(P<0.05);且观察组BA/CA明显低于对照组,预测终身高明显高于对照组,差异有统计学意义(t=3.73、4.38,P<0.05)。治疗期间,观察组总有效率92.11%(35/38)明显高于对照组总有效率77.50%(31/41),差异有统计学意义(χ^(2)=6.87,P<0.05)。结论滋阴泻火方联合亮丙瑞林能有效减轻ICPP患儿症状,调节激素水平抑制第二性征发育,控制早熟症状,提高临床疗效,有利于提高女患儿身高生长潜能,改善成年终身高。展开更多
基金Supported by a grant from the State Key Laboratory of Environmental Chemistry and Ecotoxicology,Chinese Academy of Sciences(No.KF2011-12)
文摘Objective： We aimed to evaluate the efficiency of serum testosterone suppression as well as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres for patients with metastatic prostate cancer. Methods： A total of 23 patients with metastatic prostate cancer were enrolled in the prospective study and received 6 monthly intramuscular depot injections of domestic substitute of leuprorelin acetate microspheres. Their levels and patterns of serum testosterone suppression and the potential for agonistic stimulation of serum testosterone were monitored following injection monthly （3.75 rag） depot formulation of domestic substitute of leuprorelin acetate microspheres for 24 weeks. Results： Mean testosterone was 431.4 ng/dL, 119.3 ng/dL, 28.2 ng/dL by week 1, 2, 3 and decreased to less than 15.6 ng/dL by week 4 where it remained throughout the treatment period. Median time to suppression of serum testosterone was 20.7 days. No transient minor ＂escape＂ from suppression occurred in all patients which was defined as a single testosterone value greater than 50 ng/dL once suppression was achieved. Assessment of agonistic stimulation following the second depot injection revealed no pattern of stimulation. Conclusion： We concluded that monthly （3.75 mg） depot formulation of domestic substitute of leuprorelin acetate microspheres could provide persistent, stable suppression of serum testosterone throughout the dosing intervals, and that the initial depot injection of this formulation also could provide sufficient pituitary desensitization to prevent agnostic stimulation of serum testosterone during chronic treatment.
文摘Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin®conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.
文摘Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.
