Infertility, which is defined as the failure to obtain a clinical pregnancy after at least 12 months of regular unprotected sexual intercourse, can be due to male factors in about 20-70% of cases, alone or in combination with female factors. The effects of many medications (i.e. chemotherapeutic agents, antihypertensive, 5alpha-reductase inhibitors, antibiotics and psychotropic drugs) on male reproductive system have been evaluated in several studies, with not univocal results. Psychotropic drugs are a heterogeneous group of medications with demonstrated negative effects on sexual function. Previous studies investigated the possible impact of some classes of psychotropics on semen alterations. In men, the most significant reproductive effects of psychotropics are on (1) increased PRL and gonadotropin levels with decreased testosterone; (2) sexual dysfunction, including negative effects on erection and ejaculation; and (3) decreased semen quality. Few in vitro and in vivo studies investigated the toxic effects of psychotropics in semen, showing a reduced sperm quality or increased DNA fragmentation associated with some classes of antidepressants and mood stabilizers. However, studies in humans are limited with no reported semen drugs levels and toxic mechanisms remains to be clarified.
Several classes of psychotropic drugs have been associated with an impairment in men fertility and a direct gonadotoxic effect has been reported by in vitro and in vivo studies in animals and humans (1). Although hormonal and sexual side effects of psychotropics are frequently related to their mechanisms of action, the pathophysiology of seminal toxicity remains unclear. In fact, only few studies on male reduced fertility have been conducted in patients treated with psychotropics reporting seminal alterations with some classes of antidepressants, mood stabilizers, benzodiazepines and antipsychotics. Nevertheless, a direct toxic activity on spermatozoa might be only hypothesized based on in vitro and animal studies on psychotropics gonadotoxic effects. Therapeutic Drug Monitoring (TDM), routinely used for the evaluation of serum drug levels, might improve the understanding of pathophysiological mechanisms and the clinical monitoring of male infertility of patients treated with psychotropics. In fact, seminal assessment of actual drug levels and their potential correlation with spermatozoa changes might lead to the first demonstration of a gonadotoxic effects of psychotropics in humans. Moreover, single psychotropics and different dosages most associated with seminal alterations might be identified by routine TDM and seminal coupled analysis. Therefore, the results of this study will potentially change the indications of psychiatric treatments in adult males looking for a conception by the identification of the more gonadotoxic molecules. Moreover, based on our preliminary results in a restricted group of treated patients, a minority of the studied medications seems to be not transported in seminal fluid and might constitute first-line treatments in male partners of infertile couples. Additionally, in case of patients to be newly treated with identified toxic compounds, the cryopreservation of seminal fluid in liquid nitrogen might be used to preserve sperm quality. A minor impact of psychotropics on male fertility might also improve patients' compliance to treatment in a population where a high rate of non-adherence is already reported. In conclusion, this will be the first study reporting seminal psychotropic drug concentrations and their relation with spermatozoa alterations. Semen TDM might represent a new pivotal tool in clinical management of reduced fertility in males treated with psychotropic medications.
Reference
1. Drobnis EZ, Nangia AK. Psychotropics and Male Reproduction. Adv Exp Med Biol. 2017;1034:63-101