Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones
Background: Acetaminophen (paracetamol) is one of the most common medications used for management of pain in the world. There is lack of consensus about the mechanism of action, and concern about the possibility of adverse effects on reproductive health. Methods: We first established the metabolome...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-02-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418300379 |
| _version_ | 1819025190886047744 |
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| author | Isaac V. Cohen Elizabeth T. Cirulli Matthew W. Mitchell Thomas J. Jonsson James Yu Naisha Shah Tim D. Spector Lining Guo J. Craig Venter Amalio Telenti |
| author_facet | Isaac V. Cohen Elizabeth T. Cirulli Matthew W. Mitchell Thomas J. Jonsson James Yu Naisha Shah Tim D. Spector Lining Guo J. Craig Venter Amalio Telenti |
| author_sort | Isaac V. Cohen |
| collection | DOAJ |
| description | Background: Acetaminophen (paracetamol) is one of the most common medications used for management of pain in the world. There is lack of consensus about the mechanism of action, and concern about the possibility of adverse effects on reproductive health.
Methods: We first established the metabolome profile that characterizes use of acetaminophen, and we subsequently trained and tested a model that identified metabolomic differences across samples from 455 individuals with and without acetaminophen use. We validated the findings in a European ancestry adult twin cohort of 1880 individuals (TwinsUK), and in a study of 1235 individuals of African American and Hispanic ancestry. We used genomics to elucidate the mechanisms targeted by acetaminophen.
Findings: We identified a distinctive pattern of depletion of sulfated sex hormones with use of acetaminophen across all populations. We used a Mendelian randomization approach to characterize the role of Sulfotransferase Family 2A Member 1 (SULT2A1) as the site of the interaction. Although CYP3A7-CYP3A51P variants also modified levels of some sulfated sex hormones, only acetaminophen use phenocopied the effect of genetic variants of SULT2A1. Overall, acetaminophen use, age, gender and SULT2A1 and CYP3A7-CYP3A51P genetic variants are key determinants of variation in levels of sulfated sex hormones in blood. The effect of taking acetaminophen on sulfated sex hormones was roughly equivalent to the effect of 35 years of aging.
Interpretation: These findings raise concerns of the impact of acetaminophen use on hormonal homeostasis. In addition, it modifies views on the mechanism of action of acetaminophen in pain management as sulfated sex hormones can function as neurosteroids and modify nociceptive thresholds. |
| first_indexed | 2024-12-21T05:06:45Z |
| format | Article |
| id | doaj.art-f50a1382e71b46c397279b6153df984a |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-21T05:06:45Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-f50a1382e71b46c397279b6153df984a2022-12-21T19:15:08ZengElsevierEBioMedicine2352-39642018-02-0128C31632310.1016/j.ebiom.2018.01.033Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex HormonesIsaac V. Cohen0Elizabeth T. Cirulli1Matthew W. Mitchell2Thomas J. Jonsson3James Yu4Naisha Shah5Tim D. Spector6Lining Guo7J. Craig Venter8Amalio Telenti9Human Longevity, Inc., San Diego, CA, USAHuman Longevity, Inc., San Diego, CA, USAMetabolon, Inc., Durham, NC, USAMetabolon, Inc., Durham, NC, USAHuman Longevity, Inc., San Diego, CA, USAHuman Longevity, Inc., San Diego, CA, USADepartment of Twin Research and Genetic Epidemiology, King's College London, London, UKMetabolon, Inc., Durham, NC, USAHuman Longevity, Inc., San Diego, CA, USASkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USABackground: Acetaminophen (paracetamol) is one of the most common medications used for management of pain in the world. There is lack of consensus about the mechanism of action, and concern about the possibility of adverse effects on reproductive health. Methods: We first established the metabolome profile that characterizes use of acetaminophen, and we subsequently trained and tested a model that identified metabolomic differences across samples from 455 individuals with and without acetaminophen use. We validated the findings in a European ancestry adult twin cohort of 1880 individuals (TwinsUK), and in a study of 1235 individuals of African American and Hispanic ancestry. We used genomics to elucidate the mechanisms targeted by acetaminophen. Findings: We identified a distinctive pattern of depletion of sulfated sex hormones with use of acetaminophen across all populations. We used a Mendelian randomization approach to characterize the role of Sulfotransferase Family 2A Member 1 (SULT2A1) as the site of the interaction. Although CYP3A7-CYP3A51P variants also modified levels of some sulfated sex hormones, only acetaminophen use phenocopied the effect of genetic variants of SULT2A1. Overall, acetaminophen use, age, gender and SULT2A1 and CYP3A7-CYP3A51P genetic variants are key determinants of variation in levels of sulfated sex hormones in blood. The effect of taking acetaminophen on sulfated sex hormones was roughly equivalent to the effect of 35 years of aging. Interpretation: These findings raise concerns of the impact of acetaminophen use on hormonal homeostasis. In addition, it modifies views on the mechanism of action of acetaminophen in pain management as sulfated sex hormones can function as neurosteroids and modify nociceptive thresholds.http://www.sciencedirect.com/science/article/pii/S2352396418300379MetabolomeMendelian randomizationSufotransferasessult2a1 |
| spellingShingle | Isaac V. Cohen Elizabeth T. Cirulli Matthew W. Mitchell Thomas J. Jonsson James Yu Naisha Shah Tim D. Spector Lining Guo J. Craig Venter Amalio Telenti Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones EBioMedicine Metabolome Mendelian randomization Sufotransferases sult2a1 |
| title | Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones |
| title_full | Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones |
| title_fullStr | Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones |
| title_full_unstemmed | Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones |
| title_short | Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones |
| title_sort | acetaminophen paracetamol use modifies the sulfation of sex hormones |
| topic | Metabolome Mendelian randomization Sufotransferases sult2a1 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418300379 |
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