Gender differences in drug-induced precocious puberty: a real-world analysis of adverse event reports from the FDA FAERS database (2004-2024).

BACKGROUND

Precocious puberty (PP) is the early onset of secondary sexual characteristics before the typical age of puberty, which can be caused by hormonal imbalances or external factors, such as medications. Drug-induced precocious puberty (DIPP) has become a growing concern, particularly in pediatric populations. However, the impact of gender differences on DIPP risk and the challenges in drug safety assessments have not been fully explored.

OBJECTIVE

To investigate gender-specific differences in the occurrence of drug-induced precocious puberty (DIPP) and identify potential risk signals related to medication use, utilizing data from the U.S. FDA Adverse Event Reporting System (FAERS).

METHODS

Data from the FAERS database (2004-2024) were used to identify adverse event reports related to drug-induced precocious puberty. Disproportionality analysis (DPA) was applied to detect potential signals of DIPP. The analysis considered demographic variables, including drug, age, gender, weight, indications, and reporting country. Only the most recent report for each unique "caseid" was retained.

RESULTS

A total of 529 reports of DIPP were identified, with a significant increase in reports from 2004 to 2024. The number of reports rose from 9 in 2004 to 53 in 2024, with an average of 40 reports per year from 2018 to 2024. The most frequently implicated drugs were testosterone (N = 88), somatropin (N = 52), and methylphenidate (N = 49). Drugs with the highest Reporting Odds Ratios (RORs) included mitotane (ROR = 220.35), mecasermin (ROR = 145.42), and clomifene (ROR = 141.35). Gender differences were observed, with 56.9% of reports from females and 36.3% from males. The majority of reports came from developed countries, with the U.S. contributing 50.47% of cases. The median time to adverse event occurrence was 238 days, with males showing a median induction time of 192.5 days and females at 242 days, though no statistically significant difference in induction time between males and females was found (p > 0.05).

CONCLUSIONS

Drug-induced precocious puberty presents a significant clinical concern, particularly in pediatric populations. Gender-specific differences in drugs associated with precocious puberty highlight the need for personalized drug safety assessments. Key drugs associated with DIPP, but not listed as risk factors in labeling, underscore the importance of long-term monitoring. Further research is necessary to explore the mechanisms behind gender differences and enhance drug safety strategies, particularly for children and adolescents.