Andrology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
International Consortium for Mood Psychotic and Mood Disorders Research, McLean Hospital, Belmont, MA, United States.
Front Endocrinol (Lausanne). 2021 Mar 11;12:620936. doi: 10.3389/fendo.2021.620936. eCollection 2021.
The aim of this observational study was to develop a new quantitative liquid chromatography-mass spectrometry (LC-MS/MS) method for Therapeutic-Drug-Monitoring (TDM) of psychotropic drugs in seminal fluid to investigate potential gonadotoxic effects in patients with reduced fertility. After the validation of the LC-MS/MS method for psychotropics' levels determination in seminal fluid, we included 20 male partners of infertile couples with idiopathic and/or unexplained male infertility, treated with psychotropic medications for more than 3 months and 10 untreated fertile controls. General and andrological clinical examination, semen analysis and seminal drugs, and metabolites levels determination were performed for each subject. Of the 20 patients included, 6 were treated with antidepressants; 4 with benzodiazepines and 10 with antipsychotics. Seminal drugs and metabolites levels were detectable in all samples. In particular, alprazolam, olanzapine, and levetiracetam showed seminal and serum similar concentrations, while fluoxetine, quetiapine, and aripiprazole were detectable, but seminal levels were significantly lower than the serum therapeutic range. Sperm progressive motility was significantly reduced in subjects treated with psychotropic drugs compared to the untreated controls (p = 0.03). Sperm concentration and progressive motility were significantly reduced in subjects treated with antipsychotics compared to the untreated controls and to the other classes of psychotropics (p < 0.05). In conclusion, this study reports a validated LC-MS/MS method for the detection of seminal psychotropic levels and preliminary data suggesting a potential correlation of seminal psychotropics with alterations of sperm concentration and motility. Pending larger studies, semen TDM might represent a new pivotal tool in the clinical management of reduced fertility in males treated with psychotropic medications.
本观察性研究旨在开发一种新的定量液相色谱-质谱（LC-MS/MS）方法，用于检测精液中精神药物的治疗药物监测（TDM），以研究具有降低生育能力的患者中潜在的性腺毒性作用。在对 LC-MS/MS 方法进行精神药物在精液中水平测定的验证后，我们纳入了 20 名接受精神药物治疗超过 3 个月且未经治疗的有生育能力的对照组的特发性和/或不明原因男性不育的男性伴侣。对每个受试者进行一般和男科临床检查、精液分析和精液药物及代谢物水平测定。在纳入的 20 名患者中，6 名接受抗抑郁药治疗；4 名接受苯二氮䓬类药物治疗，10 名接受抗精神病药治疗。所有样本均可检测到精液中的药物和代谢物水平。特别是阿普唑仑、奥氮平和左乙拉西坦在精液和血清中具有相似的浓度，而氟西汀、喹硫平和阿立哌唑可检测到，但精液水平明显低于血清治疗范围。与未经治疗的对照组相比，接受精神药物治疗的受试者的精子前向运动能力显著降低（p = 0.03）。与未经治疗的对照组和其他类别的精神药物相比，接受抗精神病药治疗的受试者的精子浓度和前向运动能力显著降低（p < 0.05）。总之，本研究报道了一种检测精液中精神药物水平的验证 LC-MS/MS 方法，并提供了初步数据表明，精液中精神药物可能与精子浓度和活力的改变有关。在进行更大规模的研究之前，精液 TDM 可能代表一种新的重要工具，可用于管理接受精神药物治疗的男性生育能力降低的临床情况。
