The Real-World Safety Profile of Hydroxyprogesterone: A Pharmacovigilance Study Based on the Food and Drug Administrationʼs Adverse Event Reporting System Database

Abstract

This study aimed to explore the spectrum of adverse events associated with hydroxyprogesterone and provide a comprehensive understanding of the drug’s safety profile based on the Food and Drug Administrationʼs Adverse Event Reporting System database.

Adverse events associated with hydroxyprogesterone were extracted from the Food and Drug Administrationʼs Adverse Event Reporting System database, covering the period from the first quarter of 2004 to the second quarter of 2025. Disproportionality analysis methods were used to detect potential safety signals related to hydroxyprogesterone. We further analyzed the demographic characteristics of the population and the onset time of adverse events.

A total of 40,450 adverse event reports related to hydroxyprogesterone were included, corresponding to 197 significant preferred terms categorized into 21 system organ classes per Medical Dictionary for Regulatory Activities criteria. In addition to commonly observed adverse events, several clinically relevant adverse events not previously documented were identified, including fetal distress syndrome, abnormal fetal heart rate deceleration, neonatal jaundice, neonatal respiratory distress, and low birth weight infant. The median time to the onset of hydroxyprogesterone-induced adverse events was 20 days (interquartile range: 0–72 d), with 57.8% of adverse events occurring within the initial 30 days following hydroxyprogesterone administration.

In this study, we identified both clinically observed adverse events and potential safety signals associated with hydroxyprogesterone. These results provide valuable evidence to support clinical monitoring, safety risk identification, and the development of subsequent safety investigations.