{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:46:11Z","timestamp":1793814371693,"version":"4.6.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>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\u2019 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 &amp;lt; 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.<\/jats:p>","DOI":"10.3389\/fendo.2021.620936","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T09:46:11Z","timestamp":1615455971000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Psychotropic Drugs Levels in Seminal Fluid: A New Therapeutic Drug Monitoring Analysis?"],"prefix":"10.3389","volume":"12","author":[{"given":"Rossella","family":"Mazzilli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Curto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"De Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Olana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Capi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Salerno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Cipolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Zamponi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Mazzilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Simmaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Lionetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"B1","volume-title":"Laboratory manual for the Examination and processing of human semen","year":"2010"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4081\/aiua.2013.1.20","article-title":"Impact of long-term and short-term therapies on seminal parameters","volume":"85","author":"Elia","year":"2013","journal-title":"Arch Ital Urol Androl"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12366","article-title":"The impact of drugs on male fertility: a review","volume":"5","author":"Semet","year":"2017","journal-title":"Andrology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.1600-0047.2004.00331.x","article-title":"Psychotropic drug utilization in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project","volume":"109","author":"Alonso","year":"2004","journal-title":"Acta Psychiatr Scand"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3826","article-title":"Use of psychotropic medications in S\u00e3o Paulo Metropolitan Area, Brazil: pattern of healthcare provision to general population","volume":"24","author":"Campanha","year":"2015","journal-title":"Pharmaco Epidemiol Drug Saf"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4081\/aiua.2018.1.44","article-title":"Erectile dysfunction in patients taking psychotropic drugs and treated with phosphodiesterase-5 inhibitors","volume":"9","author":"Mazzilli","year":"2018","journal-title":"Arch Ital Urol Androl"},{"key":"B7","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/978-3-319-69535-8_8","article-title":"Psychotropics and Male Reproduction","volume":"1034","author":"Drobnis","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12184","article-title":"Use of selective serotonin reuptake inhibitors reduces fertility in men","volume":"4","author":"N\u00f8rr","year":"2016","journal-title":"Andrology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.01.078","article-title":"The spermicidal and antitrichomonas activities of SSRI antidepressants","volume":"16","author":"Kumar","year":"2006","journal-title":"Bioorg Med Chem Lett"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.07.034","article-title":"Sperm DNA damage and semen quality impairment after treatment with selective serotonin reuptake inhibitors detected using semen analysis and sperm chromatin structure assay","volume":"180","author":"Safarinejad","year":"2008","journal-title":"J Urol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3089","article-title":"Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats","volume":"35","author":"Cavariani","year":"2015","journal-title":"J Appl Toxicol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.04.039","article-title":"Adverse effect of paroxetine on sperm","volume":"94","author":"Tanrikut","year":"2010","journal-title":"Fertil Steril"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3109\/01480545.2011.642382","article-title":"Genotoxic evaluation for the tricyclic antidepressant drug, amitriptyline","volume":"35","author":"Hassanane","year":"2012","journal-title":"Drug Chem Toxicol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181115","article-title":"Seminal plasma metabolomics approach for the diagnosis of unexplained male infertility","volume":"12","author":"Qiao","year":"2017","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0272.1999.00276.x","article-title":"Application of the upgraded image superimposition system (SIAS) to the assessment of sperm kinematics","volume":"31","author":"Mazzilli","year":"1999","journal-title":"Andrologia"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2009.46","article-title":"Human semen hyperviscosity: prevalence, pathogenesis and therapeutic aspects","volume":"11","author":"Elia","year":"2009","journal-title":"Asian J Androl"},{"key":"B17","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1055\/s-0037-1600991","article-title":"Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017","volume":"51","author":"Hiemke","year":"2018","journal-title":"Pharmacopsychiatry"},{"key":"B18","article-title":"Effects of carbamazepine on semen parameters in men with newly diagnosed epilepsy","volume":"14","author":"Asadi-Pooya","year":"2015","journal-title":"Iran J Neurol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12892","article-title":"Evaluation of sex hormones and sperm parameters in male epileptic patients","volume":"137","author":"Ocek","year":"2018","journal-title":"Acta Neurol Scand"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3904\/kjim.2009.24.1.1","article-title":"Overview of therapeutic drug monitoring","volume":"24","author":"Kang","year":"2009","journal-title":"Korean J Intern Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1002\/cpt.1124","article-title":"Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5-Fluorouracil Therapy","volume":"105","author":"Beumer","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1586\/17512433.2016.1172209","article-title":"Therapeutic drug monitoring of anti-infective agents in critically ill patients","volume":"9","author":"Jager","year":"2016","journal-title":"Expert Rev Clin Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000546","article-title":"Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update","volume":"40","author":"Patsalos","year":"2018","journal-title":"Ther Drug Monit"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31811fef29","article-title":"Semen quality and drug concentrations in seminal plasma of patients using a didanosine or didanosine plus tenofovir containing antiretroviral regimen","volume":"29","author":"Lowe","year":"2007","journal-title":"Ther Drug Monit"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.620936\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T09:46:13Z","timestamp":1615455973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.620936\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,11]]},"references-count":24,"alternative-id":["10.3389\/fendo.2021.620936"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.620936","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,11]]},"article-number":"620936"}}