Aim: To study the effect of testosterone undecanoate (TU) injection on spermatogenesis in rats. Methods:Twenty adult SD rats received vehicle or TU (8 mg/kg, 19 mg/kg or 625 mg/kg) injection, im, every 15 days for 60d...Aim: To study the effect of testosterone undecanoate (TU) injection on spermatogenesis in rats. Methods:Twenty adult SD rats received vehicle or TU (8 mg/kg, 19 mg/kg or 625 mg/kg) injection, im, every 15 days for 60days, and another 38 animals received similar treatments for 130 days with half of them undergoing a recovery phase of120 days (5 rats for each treatment). At the end of the treatment, testes were removed and the diameter of the seminif-erous tubules and the number of late elongated spermatids (steps 15-19) per testis were estimated with stereologicalmethods as a measure of the spermatogenic efficiency. Results: Low dose (8 mg/kg) TU treatment virtually hadno effect on spermatogenesis. A dose of 19 mg/kg slightly suppressed spermatogenesis 60 days after treatment, and se-vere suppression occurred after another 70 days of dosing. Spermatogenesis was completely recovered at the end of therecovery phase. Large dose (625 mg/kg) TU treatment did not significantly affect spermatogenesis and was well toler-ated by animals. Conclusion: TU injection reversibly suppresses spermatogenesis in rats.展开更多
Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used f...Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.展开更多
Aim: To study the anti-spermatogenic mechanism of supra-physiological doses of testosterone undecanoate (TU).Methods: Twenty fertile adult men received four intramuscular injections of TU at monthly intervals, 1000 mg...Aim: To study the anti-spermatogenic mechanism of supra-physiological doses of testosterone undecanoate (TU).Methods: Twenty fertile adult men received four intramuscular injections of TU at monthly intervals, 1000 mg uponadmission and 500 mg for the subsequent injections. The apoptotic germ cells in the semen were studied under light mi-croscope with tenninal deoxynucleotidyl tmnsferase-mediated dUTP-biotin nick end labeling (TUNEL) and Wright-Giem-sa staining methods. Results: After treatment, the sperm density and the number of spermatogenic cells in the semenwere significantly decreased ( P < 0.01), while the apoptotic ratios of spermatocytes and spermatids increased significantly( P <0.01) as compared with the pretreatment levels. Apoptosis was found to be augmented in the whole series of castoffspennatogenic cells. Conclusion: Besides its suppressive effect on spermatogenesis through a negative feed-backmechanism, TU enhances apoptosis of spermatogenic cells, which may be an additional mechanism of its anti-spermato-genic activity. ( Asian J Androl 1999 Sep; 1: 155 - 158)展开更多
Objective To investigate possible causes resulting in the differences in the spermatogenesis suppression on individual treated with levonorgestrel (LNG) implants and testosterone undecanoate (TU) injectableMethods Tot...Objective To investigate possible causes resulting in the differences in the spermatogenesis suppression on individual treated with levonorgestrel (LNG) implants and testosterone undecanoate (TU) injectableMethods Totally 21 Chinese male volunteers were given treatment with LNG implants (four rods, 75 mg/rod) and intramuscular injection of TU (500 mg,bimonthly for 3 times). According to the effects of treatment, they were divided into two groups, namely, azoospermia group (group A) and oligozoospermia group (group O). Then seminal FSH, LH, T and estradiol (E2) were determined by immunoenzymetric assay, while seminal and serum dihydrotachysterol (DHT) and serum sex hormone binding globulin (SHBG) were by radioimmunoassay, and seminal transferrin (Tf) by scatter turbidimetry assay.Results Seminal FSH, LH and serum DHT, SHBG, FTI (T/SHBG ×100) levels were significantly lower in group A than in group O, while higher seminal concentrations ofE2 were observed in azoospermia group.Conclusion The differences in the spermatogenic suppression in Chinese men might be attributed to different rate of peripheral androgen metabolism, variations in serum SHBG levels, 5á-reductase activity and individual aromatase activity during LNG plus TU administration. In addition, seminal sex hormones might be more sensitive indexes to assess the extent of feedback inhibition on hypothalamus-pituitary-testis with exogenous testosterone plus progestogen in the efficacy hormone male contraceptive trials.展开更多
The mechanism of antifertility effect of testosterone undecanoate on male rat was investigated. Eight 12-week old rats were injected with 20 mg/kg of testosterone undecanoate at bi--week intervals for 3 months. As com...The mechanism of antifertility effect of testosterone undecanoate on male rat was investigated. Eight 12-week old rats were injected with 20 mg/kg of testosterone undecanoate at bi--week intervals for 3 months. As compared to that in the 10 control rafs, the sperm density in testis rete fluid of the treatment rats declined by 7%, the motility of sperm from epididymis cauda reduced to 6%. While the testosterone level in serum increased to 255 %, the testosterone level in testis rete fluid decreased to 55%. All of these differences were significant. The androgen receptor gene expression in the testis and epididymis was suppressed in the treatment group. The decrease in output of the sperm and sperm motility of epididymis cauda may be due to the reduced testosterone production by Leydig cells and suppression of androgen receptor gene expression in testis and epididymis.展开更多
The purpose of this study was to use a kind of safe,long acting and reversible hormonal regimen for male contraception .The studied regimen was a subdermal insertion of a two rod implant (Sino implant, each rod c...The purpose of this study was to use a kind of safe,long acting and reversible hormonal regimen for male contraception .The studied regimen was a subdermal insertion of a two rod implant (Sino implant, each rod containing 75 mg levenorgestrel LNG) in each subject's forearm, followed 3 weeks after by monthly injection of TU (Testosterone Undecanoate 250 mg) for 3 months. Eighteen weeks after implantation, the Sino implant was removed. There were altogether 16 male volunteers recruited in the entire research program. Among them 6 cases reached azoospermia; one case reached oligozoospermia (sperm density <3 million/ml); 5 cases' sperm density declined greatly, the lowest to be 5.7±1.3 million/ml; the other four cases' sperm density also declined, but remained within normal range (above 20 million/ml), the lowest to be 24.5±9.0 million/ml. The duration to reach azoospermia was 16.7±0.5 weeks. The duration to resume to normal range of sperm density was 8.2±2.5 weeks in the subjects with azoospermia and oligozoospermia. In the first two weeks after insertion the LNG release of Sino implant's mean serum LNG level was about 0.38 ng/ml, in the rest of the time the LNG levels in blood was rather constant about 0.24 ng/ml. Routine analyses of blood and urine, liver and kidney functions, and blood chemistry including those parameters (TG,TC,HDL C,LDL C) of lipid metabolism didn't change much throughout the research. All the subjects' libido and sex function were well kept. Clinical observation didn't show any other adverse effects during the research.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves ins...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.展开更多
目的:探讨睾酮替代治疗对糖尿病合并迟发性性腺功能减退患者胰岛素抵抗的作用及其临床疗效。方法:82例糖尿病合并迟发性性腺功能减退患者随机分为睾酮治疗组(n=42)和对照组(n=40),两组患者均维持原有降糖、调脂治疗方案,治疗组在此基础...目的:探讨睾酮替代治疗对糖尿病合并迟发性性腺功能减退患者胰岛素抵抗的作用及其临床疗效。方法:82例糖尿病合并迟发性性腺功能减退患者随机分为睾酮治疗组(n=42)和对照组(n=40),两组患者均维持原有降糖、调脂治疗方案,治疗组在此基础上予十一酸睾酮胶丸口服,共治疗6个月,观察两组治疗前后体重指数、腰围、血糖、血脂谱、胰岛素敏感性、生殖激素以及中老年男性症状问卷(AMS)评估的相关症状评分及IIEF-5评分变化。结果:与治疗前相比,治疗组干预后体重指数(26.71±2.39 vs 25.15±2.28,P<0.05)、腰围(cm)(89.96±9.13 vs 85.03±9.58,P<0.05)、糖化血红蛋白(%)(7.73±1.31 vs 7.01±1.25,P<0.05)、甘油三酯(mmol/L)(1.97±0.83 vs 1.41±0.69,P<0.05)显著下降,总睾酮(μmol/L)(7.16±2.21 vs 14.22±2.63,P<0.05)显著升高,稳态模型评估的胰岛素抵抗指数(3.76±1.18 vs 2.55±1.03,P<0.05)和胰岛素敏感指数(96±51 vs 138±53,P<0.05)显著改善,AMS心理和躯体评分显著改善(P<0.05),但IIEF-5评分(13.28±6.38 vs14.95±6.08,P>0.05)改善不明显。结论:睾酮替代治疗可以改善糖尿病合并迟发性性腺功能减退患者胰岛素抵抗并具有确切临床疗效。展开更多
基金Financially supported by a"9th five-year" National Key Grant of Science and Technology (Grant number:969040401),and by Sichuan Committee of Education.
文摘Aim: To study the effect of testosterone undecanoate (TU) injection on spermatogenesis in rats. Methods:Twenty adult SD rats received vehicle or TU (8 mg/kg, 19 mg/kg or 625 mg/kg) injection, im, every 15 days for 60days, and another 38 animals received similar treatments for 130 days with half of them undergoing a recovery phase of120 days (5 rats for each treatment). At the end of the treatment, testes were removed and the diameter of the seminif-erous tubules and the number of late elongated spermatids (steps 15-19) per testis were estimated with stereologicalmethods as a measure of the spermatogenic efficiency. Results: Low dose (8 mg/kg) TU treatment virtually hadno effect on spermatogenesis. A dose of 19 mg/kg slightly suppressed spermatogenesis 60 days after treatment, and se-vere suppression occurred after another 70 days of dosing. Spermatogenesis was completely recovered at the end of therecovery phase. Large dose (625 mg/kg) TU treatment did not significantly affect spermatogenesis and was well toler-ated by animals. Conclusion: TU injection reversibly suppresses spermatogenesis in rats.
文摘Testosterone （T） as a compound for treatment of T deficiency has been available for almost 70 years, but the pharmaceutical formulations have been less than ideal. Traditionally, injectable T esters have been used for treatment, but they generate supranormal T levels shortly after the 2-3 weekly injection interval. T levels then decline very rapidly, becoming subnormal during the days preceding the next injection. The rapid fluctuations in plasma T are subjectively experienced as disagreeable. T undecanoate （TU） is a new injectable T preparation with a considerably better pharmacokinetic profile. After two initial injections separated by a 6-week interval, the following intervals between two injections are generally 12 weeks, eventually amounting to a total of four injections per year. Plasma T levels with this preparation are nearly always in the range of normal men, as are its metabolic products estradiol and dihydrotestosterone （DHT）. It reverses the effects of hypogonadism on bone and muscle and metabolic parameters, and on sex functions. It is suitable for male contraception. Its safety profile is excellent because of the continuous normalcy of plasma T levels. No polycythemia has been observed and no adverse effects on lipid profiles. Prostate safety parameters are well within reference limits. TU is a valuable treatment option of androgen deficiency.
文摘Aim: To study the anti-spermatogenic mechanism of supra-physiological doses of testosterone undecanoate (TU).Methods: Twenty fertile adult men received four intramuscular injections of TU at monthly intervals, 1000 mg uponadmission and 500 mg for the subsequent injections. The apoptotic germ cells in the semen were studied under light mi-croscope with tenninal deoxynucleotidyl tmnsferase-mediated dUTP-biotin nick end labeling (TUNEL) and Wright-Giem-sa staining methods. Results: After treatment, the sperm density and the number of spermatogenic cells in the semenwere significantly decreased ( P < 0.01), while the apoptotic ratios of spermatocytes and spermatids increased significantly( P <0.01) as compared with the pretreatment levels. Apoptosis was found to be augmented in the whole series of castoffspennatogenic cells. Conclusion: Besides its suppressive effect on spermatogenesis through a negative feed-backmechanism, TU enhances apoptosis of spermatogenic cells, which may be an additional mechanism of its anti-spermato-genic activity. ( Asian J Androl 1999 Sep; 1: 155 - 158)
文摘Objective To investigate possible causes resulting in the differences in the spermatogenesis suppression on individual treated with levonorgestrel (LNG) implants and testosterone undecanoate (TU) injectableMethods Totally 21 Chinese male volunteers were given treatment with LNG implants (four rods, 75 mg/rod) and intramuscular injection of TU (500 mg,bimonthly for 3 times). According to the effects of treatment, they were divided into two groups, namely, azoospermia group (group A) and oligozoospermia group (group O). Then seminal FSH, LH, T and estradiol (E2) were determined by immunoenzymetric assay, while seminal and serum dihydrotachysterol (DHT) and serum sex hormone binding globulin (SHBG) were by radioimmunoassay, and seminal transferrin (Tf) by scatter turbidimetry assay.Results Seminal FSH, LH and serum DHT, SHBG, FTI (T/SHBG ×100) levels were significantly lower in group A than in group O, while higher seminal concentrations ofE2 were observed in azoospermia group.Conclusion The differences in the spermatogenic suppression in Chinese men might be attributed to different rate of peripheral androgen metabolism, variations in serum SHBG levels, 5á-reductase activity and individual aromatase activity during LNG plus TU administration. In addition, seminal sex hormones might be more sensitive indexes to assess the extent of feedback inhibition on hypothalamus-pituitary-testis with exogenous testosterone plus progestogen in the efficacy hormone male contraceptive trials.
文摘The mechanism of antifertility effect of testosterone undecanoate on male rat was investigated. Eight 12-week old rats were injected with 20 mg/kg of testosterone undecanoate at bi--week intervals for 3 months. As compared to that in the 10 control rafs, the sperm density in testis rete fluid of the treatment rats declined by 7%, the motility of sperm from epididymis cauda reduced to 6%. While the testosterone level in serum increased to 255 %, the testosterone level in testis rete fluid decreased to 55%. All of these differences were significant. The androgen receptor gene expression in the testis and epididymis was suppressed in the treatment group. The decrease in output of the sperm and sperm motility of epididymis cauda may be due to the reduced testosterone production by Leydig cells and suppression of androgen receptor gene expression in testis and epididymis.
文摘The purpose of this study was to use a kind of safe,long acting and reversible hormonal regimen for male contraception .The studied regimen was a subdermal insertion of a two rod implant (Sino implant, each rod containing 75 mg levenorgestrel LNG) in each subject's forearm, followed 3 weeks after by monthly injection of TU (Testosterone Undecanoate 250 mg) for 3 months. Eighteen weeks after implantation, the Sino implant was removed. There were altogether 16 male volunteers recruited in the entire research program. Among them 6 cases reached azoospermia; one case reached oligozoospermia (sperm density <3 million/ml); 5 cases' sperm density declined greatly, the lowest to be 5.7±1.3 million/ml; the other four cases' sperm density also declined, but remained within normal range (above 20 million/ml), the lowest to be 24.5±9.0 million/ml. The duration to reach azoospermia was 16.7±0.5 weeks. The duration to resume to normal range of sperm density was 8.2±2.5 weeks in the subjects with azoospermia and oligozoospermia. In the first two weeks after insertion the LNG release of Sino implant's mean serum LNG level was about 0.38 ng/ml, in the rest of the time the LNG levels in blood was rather constant about 0.24 ng/ml. Routine analyses of blood and urine, liver and kidney functions, and blood chemistry including those parameters (TG,TC,HDL C,LDL C) of lipid metabolism didn't change much throughout the research. All the subjects' libido and sex function were well kept. Clinical observation didn't show any other adverse effects during the research.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.
文摘目的:探讨睾酮替代治疗对糖尿病合并迟发性性腺功能减退患者胰岛素抵抗的作用及其临床疗效。方法:82例糖尿病合并迟发性性腺功能减退患者随机分为睾酮治疗组(n=42)和对照组(n=40),两组患者均维持原有降糖、调脂治疗方案,治疗组在此基础上予十一酸睾酮胶丸口服,共治疗6个月,观察两组治疗前后体重指数、腰围、血糖、血脂谱、胰岛素敏感性、生殖激素以及中老年男性症状问卷(AMS)评估的相关症状评分及IIEF-5评分变化。结果:与治疗前相比,治疗组干预后体重指数(26.71±2.39 vs 25.15±2.28,P<0.05)、腰围(cm)(89.96±9.13 vs 85.03±9.58,P<0.05)、糖化血红蛋白(%)(7.73±1.31 vs 7.01±1.25,P<0.05)、甘油三酯(mmol/L)(1.97±0.83 vs 1.41±0.69,P<0.05)显著下降,总睾酮(μmol/L)(7.16±2.21 vs 14.22±2.63,P<0.05)显著升高,稳态模型评估的胰岛素抵抗指数(3.76±1.18 vs 2.55±1.03,P<0.05)和胰岛素敏感指数(96±51 vs 138±53,P<0.05)显著改善,AMS心理和躯体评分显著改善(P<0.05),但IIEF-5评分(13.28±6.38 vs14.95±6.08,P>0.05)改善不明显。结论:睾酮替代治疗可以改善糖尿病合并迟发性性腺功能减退患者胰岛素抵抗并具有确切临床疗效。
