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The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the
Cecilie Hurup Hansen1, Lizette Weber Larsen1, Amalie Møller Sørensen1
1Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 OE Copenhagen, Denmark.
Abstract:
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.
Insights
Selective serotonin reuptake inhibitors (SSRIs) disrupt steroid hormone production in humans, affecting testosterone and estrogen levels. Further research is needed to understand the potential health risks for users.
Area of Science:
- Endocrinology
- Pharmacology
- Toxicology
Background:
- Selective serotonin reuptake inhibitors (SSRIs) are primary treatments for major depressive disorder (MDD).
- SSRIs are known to potentially impact the endocrine system and reproductive health.
Purpose of the Study:
- To investigate the endocrine-disrupting potential of six common SSRIs.
- To analyze the effects of SSRIs on the synthesis of major steroid hormones.
Main Methods:
- Utilized the OECD-standardized H295R human adrenocortical cell assay for in vitro testing.
- Quantified steroid hormone levels, including androgens and estrogens, using a validated LC-MS/MS method.
Main Results:
- All six SSRIs demonstrated endocrine-disrupting effects on steroidogenesis around maximum drug concentrations (Cmax).
- SSRIs consistently reduced testosterone levels through various mechanisms, including impacts on CYP17.
- A relative increase in the estrogen/androgen ratio was observed, suggesting aromatase stimulation.
Conclusions:
- SSRIs can interfere with steroid hormone production in human adrenal cells at clinically relevant concentrations.
- The findings highlight the need for further investigation into the potential endocrine-related hazards associated with SSRI use.
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