Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO, USA.
Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA.
Adv Exp Med Biol. 2017;1034:63-101. doi: 10.1007/978-3-319-69535-8_8.
Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Oxidative damage to sperm can result from prolonged residence in the male reproductive tract. The increase in ejaculatory latency seen with SSRIs likely underlies some of their negative effects on semen quality, including higher sperm DNA fragmentation, seen in all SSRIs evaluated thus far. These medications increase prolactin (PRL) levels in some men, and this is often credited with inhibitory effects on male reproduction; however, testosterone levels are generally normal, reducing the likelihood of direct HPG axis inhibition by PRL. The tricyclic antidepressants have also been shown to increase PRL levels in some studies but not in others. The exception is the tricyclic antidepressant clomipramine, which profoundly increases PRL levels and may depress semen quality. Other antidepressants modulating synaptic levels of serotonin, norepinephrine, and/or dopamine may have toxicity similar to SSRIs, but most have not been evaluated. In limited studies, norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin agonist/reuptake inhibitors (SARIs) have had minimal effects on PRL levels and on sexual side effects. Antipsychotic medications increase PRL, decrease testosterone, and increase sexual side effects, including ejaculatory dysfunction. The greatest evidence is for chlorpromazine, haloperidol, reserpine, risperidone, and thioridazine, with less effects seen with aripiprazole and clozapine. Remarkably few studies have looked at antipsychotic effects on semen quality, and this is an important knowledge gap in reproductive pharmacology. Lithium increases PRL and LH levels and decreases testosterone although this is informed by few studies. The anticonvulsants, many used for other indications, generally decrease free or bioavailable testosterone with variable effects on the other reproductive hormones. Valproate, carbamazepine, oxcarbazepine, and levetiracetam decrease semen quality; other anticonvulsants have not been investigated for this adverse reaction. Studies are required evaluating endpoints of pregnancy and offspring health for psychotropic medications.
精神药物，包括抗抑郁药、抗精神病药和抗惊厥药，都会对性功能和精液质量产生负面影响。这些不良反应在男性中各不相同，并且某些药物的影响较小，在一定程度上可以进行管理。在生殖年龄的男性中，普遍使用特定的 5-羟色胺再摄取抑制剂 (SSRIs)；而应用 SSRIs 治疗早泄会增加接受 SSRIs 治疗的年轻男性数量。精子的氧化损伤可能是由于在男性生殖道中长时间停留所致。SSRIs 延长射精潜伏期，这可能是其对精液质量产生负面影响的部分原因，包括迄今为止评估的所有 SSRIs 中都可见的更高精子 DNA 碎片化。这些药物会使一些男性的催乳素 (PRL) 水平升高，这通常归因于对男性生殖的抑制作用；然而，睾酮水平通常正常，降低了 PRL 对 HPG 轴的直接抑制作用的可能性。在一些研究中，三环类抗抑郁药也显示出增加 PRL 水平，但在其他研究中则没有。例外的是三环类抗抑郁药氯米帕明，它会显著增加 PRL 水平，并可能降低精液质量。其他调节突触水平的 5-羟色胺、去甲肾上腺素和/或多巴胺的抗抑郁药可能具有类似于 SSRIs 的毒性，但大多数尚未得到评估。在有限的研究中，去甲肾上腺素-多巴胺再摄取抑制剂 (NDRIs) 和 5-羟色胺激动剂/再摄取抑制剂 (SARIs) 对 PRL 水平和性副作用的影响最小。抗精神病药物会增加 PRL、降低睾酮并增加性副作用，包括射精功能障碍。最有证据的是氯丙嗪、氟哌啶醇、利血平、利培酮和噻吨，而阿立哌唑和氯氮平的效果较小。很少有研究关注抗精神病药物对精液质量的影响，这是生殖药理学中的一个重要知识空白。锂会增加 PRL 和 LH 水平并降低睾酮，尽管这是基于少数研究得出的。许多用于其他适应症的抗惊厥药通常会降低游离或生物利用型睾酮，对其他生殖激素的影响各不相同。丙戊酸、卡马西平、奥卡西平、左乙拉西坦会降低精液质量；其他抗惊厥药尚未对此不良反应进行研究。需要研究精神药物对妊娠结局和后代健康的影响。
