Does dipyrone exhibit (anti)estrogenic activity in vivo or in vitro?

Dipyrone is a commonly used analgesic in many countries, known for its rapid hydrolysis into active metabolites, 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA), after oral administration. Despite its widespread use, there is limited data on its potential endocrine-disrupting effects, particularly regarding estrogenic or antiestrogenic activities. This study investigates whether dipyrone and its metabolites can induce estrogenic or antiestrogenic effects using both in vivo and in vitro assays.

From: "Uterotrophic and in vitro screening for (anti)estrogenic activity of dipyrone", Toxicology Letters, Volume 352, 1 November 2021, Pages 1-8

The study found that dipyrone and its metabolites did not exhibit estrogenic or antiestrogenic activity in either in vivo or in vitro assays. In the in vivo uterotrophic assay, dipyrone did not increase uterine weight at any tested dose (50, 100, and 200 mg/kg/day), indicating the absence of estrogenic activity. Additionally, co-administration of dipyrone with ethynylestradiol (EE) did not block the estrogenic action of EE, indicating the absence of antiestrogenic activity. In the in vitro Yeast Estrogen Screening (YES) assay, dipyrone and its metabolites did not demonstrate estrogen agonistic or antagonistic properties. The conclusion is that dipyrone and its metabolites do not produce (anti)estrogenic effects in the tested models.