The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the H295R cell line.
Selective serotonin reuptake inhibitors (SSRIs) used as first line of treatment in major depressive disorder (MDD) are known to exert negative effects on the endocrine system and fertility. The aim of the present study was to investigate the possible endocrine disrupting effect of six SSRIs, fluoxetine, paroxetine, citalopram and its active enantiomer escitalopram, sertraline and fluvoxamine using the OECD standardized and validated human in vitro adrenocortical H295R cell assay. All the major steroids, including progestagens, corticosteroids, androgens and estrogens were analysed using a fully validated LC-MS/MS method. All 6 SSRIs were found to exert endocrine disrupting effects on steroid hormone synthesis at concentrations just around Cmax. Although the mechanisms of disruption were all different, they all resulted in decreased testosterone levels, some due to effects on CYP17, some earlier in the pathway. Furthermore, all SSRIs relatively increased the estrogen/androgen ratio, indicating stimulating effects on the aromatase. Our study demonstrates the potential of SSRIs to interfere with steroid production in the H295R cells around Cmaxlevels and indicates that these drugs should be investigated further to determine any hazards for the users.
Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 OE Copenhagen, Denmark. Electronic address: Cecilie.hurup@sund.ku.dk.
Cecilie Hurup
CH
Hansen
Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 OE Copenhagen, Denmark.
Lizette Weber
LW
Larsen
Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 OE Copenhagen, Denmark.
Amalie Møller
AM
Sørensen
Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 OE Copenhagen, Denmark.
Bent
B
Halling-Sørensen
Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 OE Copenhagen, Denmark.
Bjarne
B
Styrishave
D000728:Androgens / Q000378:metabolism*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism; D002460:Cell Line; D015283:Citalopram / Q000494:pharmacology; D000072497:Cytochrome P450 Family 21 / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006801:Humans; D017374:Paroxetine / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*
D000728:Androgens; D000928:Antidepressive Agents; D001141:Aromatase; D015283:Citalopram; D000072497:Cytochrome P450 Family 21; D052244:Endocrine Disruptors; D004967:Estrogens; D005473:Fluoxetine; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D013254:Steroid 17-alpha-Hydroxylase; D013256:Steroids; C561410:CYP19A1 protein, human
Citalopram; Escitalopram; Fluoxetine; Fluvoxamine; LC-MS/MS; Paroxetine; Sertraline; Steroidogenesis