最新研究发现：抗抑郁剂可导致男性不育
<span class="javascript" id="text7409749"><font class="topic">医药生命科学动态跟踪讨论版最近有一篇翻译摘要，内容涉及抗抑郁剂对男性精液中精子数量的影响，该研究结果是由美国著名的康奈尔医学中心报告的。尽管试验所涉及的患者数量太少（2人），但却也给我们大家提了个警钟。<br /><br />原文如下：<br /><br /><center><font color="#008000"><b>Antidepressants Linked to Male Infertility</b></font></center><br /><br />Date Published: Tuesday, October 24th, 2006<br /><br />Researchers at New York’s Cornell Medical Center have found a major correlation between use of antidepressants and sperm count. Men who take selective serotonin reuptake inhibitors (SSRIs) are being urged to consult closely with their doctors in order to determine a proper course of action in light of the new study, the first of its kind. Cornell’s Peter Schlegel announced the results this week at the 62nd annual meeting of the American Society for Reproductive Medicine (ASRM) in New Orleans.<br /><br />The Cornell study involved the careful monitoring of two male patients over the course of two years. Both men were treated with citalopram (Cipramil) or sertraline (Lustral) and were later found to have significantly decreased sperm counts; in fact, their sperm counts actually approached zero. Once taken off the antidepressants, both men’s sperm counts rebounded to normal levels. Researchers also found a similar connection in a dozen other patients, although not quite as dramatic as in the two featured cases.<br /><br />The SSRI class of antidepressants includes the highly popular drugs Prozac and Seroxat. Previous research had linked SSRIs to issues with ejaculation and impotency, but the effect on sperm count and fertility has never been documented before. In his presentation to the ASRM, Dr. Schlegel said he found what he termed a “strong association” between SSRIs and fertility, claiming that the drugs caused a “severe deterioration” of both sperm counts and motility.<br /><br />Dr. Schlegel believes that the problem may be connected to damage of the nerves in the vas deferens, the tube trusted with the task of delivering sperm to semen just before ejaculation. For male SSRI patients who may be considering starting or continuing a family, the results may have major ramifications. <br /><br />译文：<br /><br /><center><b>男性不育与抗抑郁剂有关</b></center><br /><br />最新研究发现使用抗抑郁剂与精子数目有较大相关性。<br />由康奈尔医学中心的Peter Schlegel博士领导的这项研究对两名男性患者进行了为期两年的仔细监测。这两名男性接受了西酞普兰或舍曲林的治疗。随后发现，他们的精子数目明显下降，事实上接近于零。当停止使用抗抑郁药，他们的精子数目反弹至正常水平。研究者还在其他十几个病人身上也发现了这个现象，尽管不如这两例效果明显。<br />抗抑郁剂的选择性5羟色胺再吸收抑制剂类包括了最普遍的百忧解和赛乐特。以前的研究表明此类药物与射精和阳痿问题有关。选择性5羟色胺再吸收抑制剂与生育力之间有很强的关联，这种药能引起明显降低精子数量和活力。这个问题可能与支配输精管的神经受损有关。<br />这项新研究结果敦促那些使用选择性5羟色胺再吸收抑制剂的男性要接受他们医生的密切随访以确定是否会带来这种副作用。在使用选择性5羟色胺再吸收抑制剂的男性患者中，可能有些正在考虑要孩子。这项实验结果对他们可能有重要意义。<br />本周，康奈尔医学中心的在奥尔良举办的美国生殖医学会第62届年会上发布了这项研究结果。</font></span> <span class="javascript" id="text7409974"><font class="topic">首先大家应该对抗抑郁剂有一个基本的认识：<br /><br />历史回顾<br /> 20世纪50年代第一个三环类抗抑郁药丙咪嗪用于治疗抑郁症以来，至今已有十类数十品种抗抑郁药广泛应用于临床。回顾抗抑郁药物发展历史：20世纪50年代~60年代主要是三环类抗抑郁药物用于临床治疗，代表药为丙咪嗪、阿米替林、多虑平。国外不少国家同时开发了上述药物的去甲基代谢物如去甲丙咪嗪、去甲替林作为有效抗抑郁药物。同时期非选择性单胺氧化酶抑制剂治疗抑郁症有效，但因其不良反应和与药物、食物相互的毒性作用，此类药物未能推广，直到80年代选择性单胺氧化酶－A可逆性抑制剂吗氯贝氨问世以后，单胺氧化酶抑制剂重又受到重视。70~80年代在中国仍以三环类抗抑郁药物为抑郁症主要治疗药物。80年代后期四环类抗抑郁药马普替林、米安舍林问世，因其不良反应较轻更适用于老年抑郁症患者。此时期新一代抗抑郁药物<b>选择性5-羟色胺再摄取抑制剂</b>在国外上市，90年代进入中国，在抑郁症的药物治疗中渐占据主要位置。此后新的药物品种如文拉法辛、米他扎平、安非他酮、达体朗等等不断地推广于临床供选择应用。</font></span><br /><br /> <span class="javascript" id="text7409998"><font class="topic"><b>选择性5-HT再摄取抑制剂（Selective Serotonin Reuptake inhibitors，SSRIs）</b><br /><br /> 包括氟西汀、帕罗西汀、舍曲林、氟伏沙明、西肽普兰，分别于20世纪80~90年代上市，此类药是目前国内外使用最为广泛的一类抗抑郁药。由于该类药物作用受体具有高度选择性，其疗效满意，其不良反应，特别是心血管和抗胆碱能样不良反应明显低于TCAs。<br /><br /> SSRIs通过阻断突触前膜受体对5-HT的再摄取而升高突触间隙5-HT浓度，增强其功能达到治疗抑郁症的作用；与其他受体作用较弱。药物对中脑缝际核--前脑皮层5-HT的作用起治疗抑郁的效果；作用于中脑--基底节通路5-HT具有治疗强迫症效果；作用于中脑--边缘系统通路5-HT治疗惊恐障碍；作用于中脑--丘脑5-HT治疗贪食症；作用于中脑--脑干通路的5-HT而影响睡眠。该类药物的不良反应也与药物作用于上述通路的5-HT有关，如***不能，激越、恶心呕吐、焦虑、失眠等。5种SSRI药物受体作用选择性有所不同。<br /><br /> SSRIs均在肝脏通过P450酶系的不同同功酶进行药物的氧化代谢。其中氟西汀、帕罗西汀是CYP2D6的强抑制剂，氟伏沙明是CYP1A2、3A4的强抑制剂；舍曲林、西肽普兰属CYP弱抑制剂。临床用药时须注意与合并用药的相互作用。舍曲林、西肽普兰的药物相互作用较小。<br /><br /> 五种SSRIs半衰期以氟西汀最长为2~3天，其活性代谢物去甲基氟西汀长达7~9天，西肽普兰36小时，舍曲林22小时，帕罗西汀21小时，氟伏沙明16小时，均可每日一次给药。<br /><br /> SSRIs的适应证主要是各类抑郁症，疗效明显0优于安慰剂，相当于TCAs。各种SSRIs之间疗效无明显差异。已经临床研究，SSRIs可以治疗强迫症、惊恐障碍、社交恐怖症等特殊类型焦虑障碍。相比于抑郁症的治疗剂量要高，疗程更长。<br /><br /> SSRIs口服给药，每日一次，可于早晨服用，用药方便。常用剂量范围：氟西汀20~60mg/d，帕罗西汀20~60mg/d，舍曲林50~150mg/d，氟伏沙明50~150mg/d，西肽普兰20~60mg/d。<br /><br />SSRIs常见不良反应为：恶心、腹泻、头晕、性功能障碍、口干、便秘、出汗等。超量服药相对安全。<br /><br />SSRIs已广泛用于临床，治疗中须注意的问题还包括：<br /><br /> 1.SSRI撤药综合征：常在停药后1~10天（通常3天）出现，多见于骤然停药时。症状持续7~14天，重新给药后约在24小时可缓解。撤药反应多在长期用药时发生，常见于用药8周左右，以帕罗西汀停药时发生较多。<br /> 临床主要表现为：疲倦、激惹、焦虑、躁动、幻觉、遗忘、多动、暴发性行为、自杀、意识模糊、失眠等。神经系统可表现为眩晕、共济失调、震颤、复视、耳鸣、丘脑性疼痛。躯体症状有恶心、呕吐、腹泻、腹痛、食欲下降、胸闷、出汗、流涕等。<br /> SSRI撤药综合征的发生机理可能与5-HT、胆碱功能变化有关。与脑内药物浓度衰减速度有一定关系。重复给药可较快缓解症状，支持疗法有益于患者，关键是缓慢减药再停药，预防为主。<br /><br /> 2.高血清素综合征：常在SSRIs与其他肝酶抑制剂和MAOIs合用时或交替使用时出现。其发生机理与药物代谢速度缓慢，血药浓度明显升高，使5-HT功能亢进引发。临床主要表现为：意识障碍，可致昏迷、不安、易激惹、恶心、呕吐、腹泻、高热、肌痉挛、反射亢进、震颤、出汗、心动过速、高血压等。<br /> 处理原则：停药、支持疗法、肌松剂的应用、降温、可给予5-HT拮抗剂噻庚啶。重视和注意药物相互作用，减少联合用药有利于预防。 </font></span><br /><br /><br /> <br /><br />在最近举行的美国泌尿学会年会上，有专家透露，全球首个治疗男性早泄的药物达泊西汀(Dapoxetine)已经完成了三期临床实验，现已送交美国食品和药品管理局(FDA)审批。如果获得批准，就意味着在不久的将来，众多患有早泄疾病的患者有了有效的治疗药物。达泊西汀如若问世，其所受关注的程度将不亚于万艾可。<br /> 早泄比ED发病率更高<br /> 早泄的危害程度一点都不亚于勃起功能障碍（简称ED），且发病率更高。统计资料显示，目前全球约有27%—34%的男性存在不同程度的早泄症状，而勃起功能障碍的发生比例只有10%到12%。勃起功能障碍一般只影响年龄较大的男性，但早泄在不同年龄的男性中都可能发生，且往往会伴随患者一生。<br /> 从医学上讲，多数男性从性交开始到射精所持续的时间平均在7.3分钟，而早泄的人这个时间为2分钟之内。美国泌尿学会的专家说，与男性勃起功能障碍相比，早泄问题没有得到应有的重视。但是，实际上早泄不仅影响患者本人的性生活质量，也影响女性的性生活满意度，夫妻关系会因之受损，甚至会损伤男性的自信心。目前，治疗早泄还没有什么有效药物。<br /> 抗抑郁药治疗早泄<br /> 达泊西汀是一种选择性5—羟色胺再吸收抑制剂，它实际上是一个在临床上用于治疗抑郁症和相关情感障碍的药物。在这个药物的使用过程中医生发现，它可以缓解患者的早泄症状。随后，一些医生开始用小剂量达泊西汀对早泄进行试探性治疗。<br /> 美国左治亚医学院泌尿科主任刘易斯认为，早泄可能是大脑性欲中心反应性过高所致，导致男性过早地射精。而大脑性欲中心存在着5—羟色胺和多巴胺之类的化学物质，它们能传导强烈的射精冲动，而达泊西汀能干扰上述化学物质，达到延迟射精时间的目的。<br /> 射精时间延后3—4倍<br /> 负责达泊西汀临床研究的是美国明尼苏达大学泌尿外科主任普赖尔。<br /> 研究人员选择了2614名早泄患者作为研究对象，这些人年龄在18岁至77岁之间。这些研究对象有人服用30毫克达泊西汀，有人服用60毫克达泊西汀，还有人使用的是安慰剂。<br /> 在进行试验前，这些研究对象75%的射精潜伏期（1994年提出的用于早泄的诊断与研究的临床指标）在2分钟之内。研究人员要求受试者在性生活前1—3个小时用药，然后记录射精潜伏期的时间。<br /> 临床研究结果显示，用药组患者，无论服用的是30毫克还是60毫克，患者对射精的控制能力和性生活满意度的比例均有较大提高。它可以使男性射精时间延后3到4倍。而且，在第一次用药后，在整个12周的研究期间这一效果始终持续着。而对照组则变化不大。<br /> 研究人员认为，达泊西汀这种药物的耐受性较好，恶心和头痛是其主要的副作用，而且使用高剂量者比使用低剂量者出现的几率要高。此外，在使用高剂量的患者中，还有少数人出现腹泻和头晕。<br /><br /><a class="ilink" href="http://www.dapoxetine.net.cn/what_is_dapoxetine.htm" target="_blank">[url]http://www.dapoxetine.net.cn/what_is_dapoxetine.htm[/url]</a> <br /><br /> <br /><br />University of Minnesota researchers have shown that the drug dapoxetine is a safe and effective drug treatment for premature ejaculation.<br /><br />The drug, dapoxetine, is a selective serotonin reuptake inhibitor (SSRI) that was developed specifically to treat premature ejaculation. SSRIs, normally used to treat depression, have been prescribed "off-label" for treatment of premature ejaculation, but those drugs need to be taken regularly in order to be effective. Dapoxetine, however, is a short-acting drug that has an effect within about one hour.<br /><br />This multicenter trial took place at 121 sites across the United States. Men in stable, heterosexual relationships took part in the trial, which divided the men into three groups.<br /><br />One group received a placebo, the second received 30 milligrams of the drug, and the third group received 60 mg of the drug. Both the study participants and medical personnel overseeing the trial were unaware who was assigned to each group. Both groups who received the drug increased their time to ejaculation.<br /><br />Jon Pryor, M.D., professor and chair of urological surgery, was the primary investigator of this clinical trial. The research will be published in the Sept. 9, 2006, issue of The Lancet.<br /><br />At the start of the study, the men ejaculated less than one minute after intercourse began. After the 12-week study, the time to ejaculation increased to 1.75 minutes for the placebo group, 2.78 minutes for the group on the lower dose, and 3.32 minutes for the higher dose. The time to ejaculation was measured by the use of a stopwatch by the men's partners.<br /><br />"Dapoxetine also improved patients' perceptions of control over ejaculation, satisfaction with sexual intercourse, and overall impression of the change in their condition," Pryor said. "The patients' partners also benefited through improved satisfaction with sexual intercourse."<br /><br />Premature ejaculation is thought to be the most common male sexual dysfunction, effecting between 21 and 33 percent of men. The underlying physical reason for PE is not well understood.<br /><br />The study was funded by ALZA Corporation, the company that developed the drug dapoxetine. Pryor has served on advisory boards for ALZA advisory boards in the past.<br /><br /><a class="ilink" href="http://www.sciencedaily.com/releases/2006/09/060910094030.htm" target="_blank">[url]http://www.sciencedaily.com/releases/2006/09/060910094030.htm[/url]</a> <br /><br /><br /><br />FRIDAY, Sept. 8 (HealthDay News) -- A new antidepressant drug designed specifically to treat premature ejaculation proved safe and effective in two large trials, researchers report.<br /><br />However, it's not likely that dapoxetine, a short-acting selective serotonin reuptake inhibitor (SSRI), will win U.S. approval anytime soon because it can produce side effects, one expert said.<br /><br />SSRIs, which are used to treat depression and other psychiatric disorders, are now also used "off-label" as a treatment for premature ejaculation. They work because one of their side effects is to delay ejaculation. But, continued SSRI use can have some negative side effects, such as psychiatric problems, skin reactions, weight gain, and loss of libido, experts said.<br /><br />"This is the first drug specifically developed for premature ejaculation," said lead researcher Dr. Jon L. Pryor, a professor and chairman of urologic surgery at the University of Minnesota. "It worked both in lengthening ejaculation time and in patients' feeling control over ejaculation and both subjects' and partners' feelings of satisfaction with intercourse," he said.<br /><br />The findings are published in the Sept. 9 issue of The Lancet.<br /><br />Premature ejaculation is the most common male sexual problem, even more common than erectile dysfunction, affecting 21 percent to 33 percent of American men.<br /><br />In the study, Pryor and his colleagues looked at the combined results of two trials that tested dapoxetine. The trials included 2,614 men who had moderate to severe premature ejaculation.<br /><br />The men were randomly assigned to receive a placebo or different doses of dapoxetine. They were told to take the drug one to three hours before having sex. At the start of the study, the men ejaculated, on average, in less than a minute after penetration.<br /><br />However, after 12 weeks, men taking dapoxetine increased their time to ejaculation to 2.78 minutes for those receiving a 30-milligram dose, and to 3.32 minutes for those receiving a 60-milligram dose, the researchers found. For men taking a placebo, the time to ejaculation averaged 1.75 minutes.<br /><br />Pryor thinks this study will get people talking more about the problem of premature ejaculation. "I hope this paper brings premature ejaculation out of the closet," he said. "I hope it allows for mature discussion about it, and that people realize that there is hope."<br /><br />One expert familiar with dapoxetine thinks the drug has promise but will not be available in the United States.<br /><br />"The problem is that dapoxetine was presented to the U.S. Food and Drug Administration last year, and they rejected it out-of-hand as a treatment for premature ejaculation," said Dr. James Barada, director of the Center for Sexual Health in Albany, N.Y.<br /><br />The drug can produce side effects such as nausea, headache, upset stomach and weakness. It is being released in Europe, Barada said.<br /><br />"Premature ejaculation is a real clinical condition that causes distress for the man, his partner and especially the relationship," he added. "Because we have no approved therapy, we are at somewhat of a loss to treat it. For many years, we have been using off-label therapies -- SSRIs -- because of the side effect they have of delaying ejaculation."<br /><br />Doctors can still use SSRIs, Viagra, and psychotherapy to treat the problem, Barada said. "We need to get better research to understand the mechanisms of premature ejaculation and hopefully design a medicine that has good efficacy and safety that is not an SSRI," he said.<br /><br /><a class="ilink" href="http://www.nlm.nih.gov/medlineplus/news/fullstory_38424.html" target="_blank">[url]http://www.nlm.nih.gov/medlineplus/news/fullstory_38424.html[/url]</a> <br /><br />页:
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