大剂量睾酮有可能作为男用避孕药

华盛顿大学医学系的 Matsumoto 等人在男用避孕药的试验中发现大约50%的男性在使用庚酸盐睾酮(TE)后出现精子缺乏症,另外50%的人的精子缺乏则更为严重。为了确定这种精子严重缺乏是否由庚酸盐睾酮所致,作者对6例正常男性作了精子功能研究。6例男性年龄为19～40岁,肌肉注射高剂量的庚酸盐睾酮,其中4例为每星期100mg,2例为300mg,用药期为5～6个月。与此同时,另5例正常男性作为对照组,以注射麻油作为安慰剂。每组在前处理期和处理3个月后均进行一次精液分析和体外精子功能评价(主要用去透明带仓鼠卵穿透试验法,HOPT)。每个受试者在禁欲48     

一种新的男性避孕药在世界范围内进入临床试验

据西雅图华盛顿大学报道一种可逆的男性睾酮避孕药睾酮庚酸盐(暂时阻止精子产生)已应用于250例男性临床试验,其避孕机理类似女性口服避孕药(通过脑垂体释放激素阻止排卵)。避孕药的初步试验表明:50～60%男子的精液中无精子。然而,Bremner的观察偶见精液中有少许精子。目前,对250例男子的临床试验将证实上述问题。该避孕药应注射使用,因为激素口服,保持活性时间短。每周注射200mg,这种避孕药并非没有副作用,尽管很小,但大多数受试者注射后,体重有少许增加。睾酮能使男性肌肉增加和钠潴留,几例出现痤疮。研究者预测:使用该药能降低男子性     

庚酸睾丸酮对正常男性的作用:多中心避孕效果研究

本文报道了在7个国家的10个研究中心分别对21～45岁的健康男性每周肌肉注射200mg庚酸睾丸酮,导致无精子症而进行男性避孕,最大规模地评估外源性睾酮对正常男性代谢及其它生理功能的影响,并比较了其它性激素男性避孕的副作用。研究对象为271人(31.8±5.4岁),其中中国人组82例(35.2±4.5岁),非华人组189例(30.3±5.1岁)。 结果:用药6月内有157例(58％)发生无精子症,另外68例(25％)未发生无精子症。46     

男性激素避孕方法研究进展

男性可采用的理想避孕方法应该具有高度的有效性、安全性、可接受性、可负担、作用时效长且有快速可复性、使用无文化背景冲突等特点。目前这样理想的避孕方法还没有,而激素避孕药是目前的研究热点,男性激素避孕的广泛应用将很快成为现实。系统总结目前男性激素避孕的常用方法,包括使用单剂睾酮、睾酮与孕激素配伍、睾酮与促性腺激素释放激素(GnRH)类似物配伍以及激素类免疫避孕,尤其是中国在男性激素避孕方面的领先研究结果,并介绍男性激素避孕的机制与研究进展。     

肌注环戊丙酸睾酮后的激素动力学

对性功能低下的男子,肌注睾酮作替代疗法是安全和有效的,庚酸睾酮(TE)和环戊丙酸睾酮(TC)作为男性激素的酯类注射剂广泛用于临床。本文研究性功能减退病人一次肌注TC200mg或长期肌注TC后14天中血睾酮(T),游离睾酮(FT),非性激素结合球蛋白睾酮(non-SHBG-T),雌二醇(E_2)和LH的变化。研究包括11例性功能低下男子,其中青年组(20～48岁)2例,中年组(46～65岁)6例,老年组(>66岁)3例,大部分为轻度性功能低下仅1例为继发于LH、FSH降低的重度性功能减退者。6例单次注射TC,5例每2周肌注TC 200mg已3个月以上。参与研究者均询问病史及全面体格检查,取晨血测PRL、T、     

长效醋酸甲孕酮用于男性避孕的药代动力学及抑制精子发生的剂量研究

比较两种剂量长效醋酸甲孕酮(DMPA)用于男性避孕的药代动力学特性以及抑制精子发生的效果,推荐进一步临床试验配伍剂量和注射间隔。方法:将筛选合格的正常志愿者30名随机分成3组(每组10名),A组150mgDMPA+1000mg十一酸睾酮酯(TU);B组300mgDMPA+1000mgTU;C组单独注射1000mgTU(为对照组)。A和B组受试者按要求接受指定的配伍剂量注射。注射前后每周静脉取血,直至8周,进行血MPA测定。然后,受试者继续每8周接受指定的配伍剂量或TU单独注射,直至完成24周的治疗期,并按要求定期随访进行精液分析及其它安全性指标监测,最后完成24周的恢复期随访。结果:受试者的各项参数在各组内均匀分布。尽管B组较A组有相对较高的血药浓度,但药代动力学的各项参数在两组之间无显著性差异。A、B和C组抑制精子发生起效时间分别为80±5d、83±8d和92±6d,各组间没有统计学差异。尽管合用组比单用组有更持久地抑制精子发生的趋势,但各组之间没有统计学差异。合用组能更加有效地抑制促性腺激素的分泌,与单用组之间有显著性差异;促性腺激素的抑制程度与配伍中DMPA的剂量无关。结论:A与B组在药代动力学的各项参数与抑制精子发生的疗效上无显著性差异。150mgDMPA与1000mgTU或更长效的雄激素联合应用可能成为2～3个月肌肉注射一针的男性避孕药的最佳剂量组合。推荐使用低剂量DMPA配伍TU进行临床避孕有效性的研究。     

外源性睾酮抑制精子发生机制的研究

目的研究外源性睾酮对健康成年男性精子数量和功能的影响，评价外源性雄激素对精子的抑制作用。方法40名有生育能力的健康成年男性志愿者随机分为2组，每组20人，治疗处理如下。十一酸睾酮（TU）组：TU1000mg IM（首剂剂量），然后每6个星期500mg IM共2次，是分别在治疗期第6周和第12周，之后无继续治疗措施；对照组：同期注射等体积生理盐水。结果首次TU注射后精子计数逐渐减少，但相对较慢，在第6周时平均精子计数降低到62．4（平均仅减少了14．9％，19．3％）×10^6／ml；在第18周时才达到最大的抑制，平均精子计数降低到3.8（平均减少了63．5％，95．1％）×10^6／ml。在恢复期结束，所有各组的平均精子计数均恢复到〉20×10^6／ml的水平。TU注射之后，血总T和游离T水平均升高，然后恢复正常。结论外源性雄激素能够抑制精子发生，结果具有可逆性，对部分蛋白质功能的进一步研究，将为男性激素避孕机制的研究提供更多信息。     

枸橼酸克罗米芬对男子不育症的疗效

不育夫妇中50%系因男性生育机能障碍,这些人中大多可发现精子数减少,迄今尚无治疗特发性男子不育的方法,枸橼酸克罗米芬(CC)为常用的治疗男子不育的药物,自60年代开始用于临床,一般为25～100mg/天,连续用2～6个月。一些报告认为 CC 可增加精子计数和妊娠率,但另一些报告认为不能改善生育力。本文中作者用双盲法比较了安慰剂和 CC 对特发性精子减少的不育男子精子计数和生育力的影响。研究包括23例23～49岁男子,无全身疾病及精神病,夫妇未行避孕,但一年未孕。参与研究对象均符合下列条件:①三次精液检查精子计数为50～2000万/ml,精子形态正常,活力>10%;②血清黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)和催乳激素(PRL)正常;③裉据病史、体检、基础体温、月经史、血孕酮(P)水平、输卵     

睾丸热压内裤研制及对精子发生影响的临床研究

目的:研制适用于人用睾丸热压内裤(THU),并观察其对精子发生的影响。方法:恒温控制器、定时器、交流电变压装置及热压内裤的设计和研制,9例已育成年健康男性志愿者,每周穿THU2次,每次穿50min,3个月为1个实验周期。在实验前、中、后分别取精液和血液,以穿THU前的相关指标作自身对照,实验期分别于1个月、2个月和3个月观察,恢复期分别于1个月、2个月、3个月和6个月观察随访。结果:恒温控制器温度43℃±0.5℃,定时器0～60min,输入电压220V,输出电压12V,穿THU2个月后,精液常规中精子密度和精子活动率明显下降,而畸形精子比率明显升高;3个月后,精子密度和精子活动率进一步明显下降,9例受试者精子密度均下降到20×106/ml以下,3例<5×106/ml,其中有1例2×106/ml;在恢复期2个月、3个月和6个月后,上述各项指标又恢复到实验前水平。血清T、FSH、LH实验前后无明显改变。结论:THU对精子发生抑制效果较为明显,可考虑与男性激素合用抑制精子发生而达到避孕目的。     

Danazol治疗子宫内膜异位症—长期随访

本文报告1967～1973年49名诊断为子宫内膜异位症的妇女,使用Danazol治疗,剂量800mg/天,用药1～9个月(平均6个月)停药后25～90天(平均42天)恢复排卵性月经,随访49～126个月(平均78个月)。常规作阴道细胞学检查,对几个病人在治疗前和治疗终止时作子宫内膜活检,一些病人在治疗前、中、后每天作血清FSH和LH的分析。在用药期间,多数病人发生闭经,少数有不规则轻度阴道出血。治疗效果:41例(83.7%)客观症状明显减轻、全部病人主观症状如痛经、盆腔疼痛、性交困难、大便困难等中度至明显减轻。虽有33%病人停     

Testosterone enanthate a possible reversible male contraceptive

The effect of chronic treatment with testosterone enanthate (TE) on sperm production and plasma testosterone levels was evaluated in 16 healthy male volunteers. During the induction of azoospermia each subject received 200 mg TE twice a week for 2 weeks once a week for 2 weeks, and once every other week for a month. Subsequently an attempt was made to maintain azoospermia by administration of 200 mg TE every 3 weeks. The induction phase resulted in suppression of sperm production to azoospermia or oligospermia of less than 100,000/ml. However, the schedule of injections during the maintenance phase did not maintain the azoospermic state. Consequently, the frequency of injections for maintenance was increased to 200 mg TE every 2 weeks. This maintained sperm counts below 3 million/ml in all subjects. Thereafter the maintenance schedule was changed to 200 mg TE every 10–12 days; on this regimen, azoospermia or oligospermia of less than 100,000/ml was maintained in all subjects. Blood testosterone levels rose approximately 100% over the baseline level during the induction phase but returned to pretreatment range during maintenance phase.This study demonstrates that testosterone enanthate can induce azoospermia and maintain the azoospermic state without elevation of circulating testosterone levels outside the pretreatment range. These findings suggest the feasibility of using a testosterone preparation as an effective male contraceptive. A larger number of subjects must be evaluated to determine the exact dose requirements and the possibility of side effects subsequent to chronic administration of this steroid.     

Testosterone for male contraception during one year: attitudes, well-being and quality of sex life

Men's attitudes, well-being, and sex life were studied during 1 year's use of testosterone contraception. A consecutive series of 25 men were followed by structured interviews at baseline, during the efficacy phase of oligo-azoospermia and after recovery. Open questions gave qualitative aspects on male contraception. Themes obtained were expectations about freedom and control over their reproduction (16/25) and an enhanced sex life (17/25). The method was rated to be as expected or better by the great majority. Health and most aspects of the men's sex life did not change, but the frequency of intercourse and the quality of sex life in general were higher (p = 0.001 and p = 0.006, respectively) during the efficacy phase compared to the recovery phase. The decrease during recovery phase may be explained by a pharmacological down-regulation of the androgen receptors. Eight of 22 men admitted slightly aggressive feelings during treatment. Five of 11 women reported the men as more self-assertive during the efficacy phase.     

Hormonal contraception in men

Over the past few decades, female hormonal contraception has been seen to be very successful. However, this has still not resulted in a hormonal contraceptive for men. Certain injectable combinations ofandrogens and progestagens have been found to suppress spermatogenesis. All combinations that have been tested so far suffer from a relative lack of efficacy, a long lag time to achieve azoospermia, requiring the user to undergo one or more semen analyses, a moderate user friendliness, and concerns about the long-term safety and reversibility. It is not to be expected that male hormonal contraception will become a serious alternative to the already existing female equivalent during the coming 5 years.     

米非司酮配伍米索前列醇用于黄体期紧急避孕临床效果观察

目的:研究女性黄体期应用小剂量米非司酮配伍小剂量米索前列醇序贯给药法进行紧急避孕的有效性、安全性和可接受性。方法:采用前瞻性临床研究,接收符合接收标准,要求避孕,并愿意参加本课题研究的248例育龄女性,按用药时所处月经周期中黄体期的早晚,分为黄体早期(81例)、黄体中期(82例)、黄体晚期(85例)3组,所有对象空腹顿服米非司酮25mg×3片,36~48h再次同法服用米索前列醇200μg×2片,预约预期下次月经后10天内随访。观察在黄体各期用药后的妊娠率、月经的变化和副作用。结果:①248例妇女,妊娠3例,失败率1.2%;②随访时245例月经已经来潮,黄体早期组开始出血时间早于其他两组,经检验差异有显著性意义(P<0.05);出血持续时间3组间无显著性差异,与正常月经经期基本一致;③应用两种药物均无不良后果,副作用轻,能自行缓解。结论:小剂量米非司酮配伍小剂量米索前列醇序贯给药用于黄体期避孕是有效、安全和可行的。     

A randomized clinical trial of the effect of intraoperative saline perfusion on postvasectomy azoospermia

BACKGROUND: We wanted to determine whether a saline flush during vasectomy would reduce the time needed to reach azoospermia. METHODS: During vasectomy men were randomly assigned to flush the prostatic end of the vas deferens with 10 mL of normal saline (intervention group, n = 50), while the remaining men (n = 56) served as controls. Sperm counts were performed on the immediate postprocedure urine specimen and on semen samples at 1, 6, and 12 weeks after vasectomy. RESULTS: The postprocedure urine specimens from the intervention and control groups contained 29.2 x 106 and 0.004 x 106 sperm, respectively (P < .001). Total sperm counts in the ejaculate for intervention and control groups at 1, 6, and 12 weeks were (in millions of sperm): 14.1 and 13.8, 0.4 and 8.0, and 0.0 and 0.011, respectively (P > .05 at all time points). There was no difference in the rate at which the men in the 2 groups achieved azoospermia. CONCLUSIONS: Vasal perfusion with saline during vasectomy was effective in removing sperm from the distal vas; however, perfusion did not increase the rate at which men achieve azoospermia.     

黄体期避孕对月经影响的临床研究

目的:评估当妇女在月经周期有无保护性生活超过120h,或多次无保护性生活后于黄体期避孕对月经的影响。方法:在黄体期1次性服用米非司酮100mg并在36~48h后服用米索前列醇400μg,服药后观察月经情况。结果:100例受试者中4例妊娠,在成功避孕的96例中,月经提前68例(70·83%),延期15例(15·6%),无改变13例(13·5%)。服药前后比较,月经周期缩短,差异有显著性意义(P<0.01),服药后月经出血天数5·76±1·18天,与妇女原来出血天数比较差异有显著性意义(P<0.05),与服药前自身经量比较,经量减少1例,相似90例,增多5例,经量与服药前差异无显著性意义(P>0.05)。服药距下次月经时间为6·85±1·88天,服药距下次月经9~7天组和6~4天组月经周期缩短,与服药前相比差异均有显著性意义(P<0.05),而3~1天组月经周期改变不明显(P>0.05);出血天数及经量3组间无显著性差异(P>0.05)。结论:黄体期避孕有效率为96%,该方法可使妇女月经周期缩短,经期延长,且服药距下次月经时间长对月经周期影响较大。     

Contraceptive efficacy of polyester-induced azoospermia in normal men.

The contraceptive effect of a polyester sling applied to the scrotum was studied in 14 men. The suspensor was worn for 12 months. Follow-up investigations comprised periodic check of semen character, testicular size, rectal-testicular temperature difference, serum reproductive hormones and testicular biopsy. The electrostatic potentials generated by friction between the polyester suspensor and the scrotal skin were determined. Female partners used contraceptives until the men became azoospermic. After 12 months, the suspensor was abandoned and the aforementioned investigations were performed again. In the suspensor-wearing period, all men became azoospermic after a mean of 139.6 +/- 20.8 sd days, with decrease in both testicular volume (P less than 0.05) and rectal-testicular temperature difference (P less than 0.001). Serum reproductive hormones showed no significant change (P greater than 0.05). Seminiferous tubules revealed degenerative changes. No pregnancy occurred during this period. The polyester suspensor generated electrostatic potentials (mean 366.4 +/- 30.5 sd volt/cm2 by day and 158.3 +/- 13.6 sd volt/cm2 by night). In the suspensor-release period, the sperm concentration returned to the pre-test level in a mean period of 156.6 +/- 14.8 sd days. Likewise, the testicular volume and rectal-testicular temperature difference were normalized. The 5 couples, who had planned to become pregnant, conceived. The azoospermic effect of the polyester sling seems to be due to two mechanisms: 1) the creation of an electrostatic field across the intrascrotal structures, and 2) disordered thermoregulation. To conclude, fertile men can be rendered azoospermic by wearing the polyester sling. It is a safe, reversible, acceptable and inexpensive method of contraception in men.     

Steroid hormones for contraception in men: systematic review of randomized controlled trials

Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so an "add-back" therapy is needed. We conducted a systematic review of all randomized controlled trials of male hormonal contraception and azoospermia. Few significant differences emerged from these trials. Levonorgestrel implants combined with injectable testosterone enanthate (100 mg im) were significantly more effective than was levonorgestrel 125 microg po daily combined with testosterone patches [10 mg/d; odds ratio (OR) for azoospermia with the oral levonorgestrel regimen, 0.03; 95% CI, 0.00-0.29]. The addition of levonorgestrel 500 microg po daily improved the effectiveness of testosterone enanthate 100 mg im weekly by itself (OR for azoospermia with the combined regimen, 4.0; 95% CI, 1.00-15.99). Several regimens, including testosterone alone and gonadotropin-releasing hormone agonists and antagonists, had disappointing results. In conclusion, no male hormonal contraceptive is ready for clinical use. All trials published to date have been small exploratory studies. As a result, their power to detect important differences has been limited and their results have been imprecise. In addition, the definition of oligospermia has been imprecise or inconsistent in many reports. To avoid bias, future trials need to pay more attention on the methodological requirements for randomized controlled trials. Trials with adequate power would also be helpful.     

Evaluation of efficacy, safety, and reversibility of combination regimen of cyproterone acetate and testosterone buciclate in bonnet monkey

A combination regimen of cyproterone acetate (CPA) and testosterone buciclate (TB) was evaluated for its contraceptive efficacy, safety, and reversibility in bonnet monkeys. Cyproterone acetate (5 mg in 0.2 mL of olive oil) injected daily for 180 days, in combination with 40 mg testosterone buciclate given i.m. on days 0, 60, and 120 in the monkeys of group II (n = 6) induced azoospermia in all animals by 120 days, which was maintained until day 210. By day 240 sperm concentration increased gradually and reached baseline values by day 330. When 5mg of cyproterone acetate was injected daily for a similar duration in combination with a higher dose (80 mg) of testosterone buciclate in the monkeys of group III (n = 6) on days 0, 60, and 120, uniform and consistent azoospermia could not be achieved and two animals remained oligozoospermic even after 180 days of treatment. Mean sperm concentration did not return to baseline values until the day that the study ended, i.e. day 330. In groups II and III serum testosterone levels were elevated (p <0.05) from days 9-120 except on day 150 and returned to near baseline values by day 330. Serum testosterone levels were higher in group III compared to group II. The sperm concentration and testosterone levels in control animals (group I; n = 6) showed fluctuations. Lipid profile and liver function parameters did not show significant changes in any group. The present data clearly indicate that administration of CPA and TB in proper dosage combination can provide an effective, safe, and reversible method of male contraception.     

LIQUID STORAGE (50C) OF RAM SEMEN IN DIFFERENT DILUENTS

This study examined the effects of three diluents - skim milk (M), TesT (TE) and Tris-trehalose (TR) - on quality of ram semen stored at 5⁰C over a long term. Percentage of motile spermatozoa (PM), motility score (MS), percentage of intact acrosomes (PIA), and percentage of swollen spermatozoa under hypoosmotic conditions (PS) were assessed after cooling and every 24 h up to day 16. There was a significant effect (p&lt;.01) of diluent type in the conservation rates after cooling for PM. The TR diluent achieved greater values (94.7+/-1.36%) than TE(82.4+/-3.08%), while M showed an intermediate value (89.3+/-2.17%). In relation to time of storage, TR diluent showed the highest PM values up to day 12, but differed (p&lt;.05) from TE medium only until day 4. The TR extender maintained a PM&gt; 50% up to day 8, while TE and M were greater than 50% up to day 5. Skim milk maintained progressive movement of sperm cells for longer (MS=3 until day 5) than the other diluents. There were no significant differences in PIA among the 3 media during the first 6 days of storage (except in day 2), and M showed the lowest value afterward. There was no significant extender effect on PS for the first 3 days, but after day 6 diluent M also showed the lowest values of this variable.