TY - JOUR
T1 - The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the H295R cell line
AU - Hansen, Cecilie Hurup
AU - Larsen, Lizette Weber
AU - Sørensen, Amalie Møller
AU - Halling-Sørensen, Bent
AU - Styrishave, Bjarne
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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 Cmax levels and indicates that these drugs should be investigated further to determine any hazards for the users.
AB - 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 Cmax levels and indicates that these drugs should be investigated further to determine any hazards for the users.
KW - Journal Article
U2 - 10.1016/j.tiv.2017.02.001
DO - 10.1016/j.tiv.2017.02.001
M3 - Journal article
C2 - 28179152
SN - 0887-2333
VL - 41
SP - 1
EP - 11
JO - Toxicology in Vitro
JF - Toxicology in Vitro
ER -