Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones.

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Cohen IV, Cirulli ET, Mitchell MW, Jonsson TJ, Yu J, Shah N, Spector TD, Guo L, Venter JC, Telenti A

Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones.

EBioMedicine. 2018 Feb;28:316-323. doi: 10.1016/j.ebiom.2018.01.033. Epub 2018 Feb 15.

PubMed ID

29398597 [ View in PubMed

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Abstract

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 35years 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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Acetaminophen	Sulfotransferase 1A1	Protein	Humans	Unknown	Substrate	Details