Sex-Specific Safety Signals of Finerenone Versus Spironolactone: Insights From the FDA Adverse Event Reporting System

Spironolactone, a non-selective mineralocorticoid receptor antagonist (MRA), frequently causes off-target hormonal effects in women. Finerenone, a selective non-steroidal MRA, may mitigate these effects, but real-world comparative data remain scarce.

This study aimed to compare adverse event reporting profiles of finerenone and spironolactone in female patients using the FDA Adverse Event Reporting System (FAERS).

We conducted a retrospective disproportionality analysis using FAERS data (January 2022-March 2026), identifying female primary suspect reports for finerenone (N = 715) and spironolactone (N = 4,651). Reporting odds ratios (ROR) with 95% confidence intervals were calculated across reproductive, endocrine, skin, and psychiatric domains. Hyperkalemia served as a positive control.

Finerenone reporters were significantly older than spironolactone reporters (350 (75.9%) vs. 2,329 (59.9%) aged 65 years and older; p < 0.0001). Spironolactone demonstrated disproportionately higher reporting across all assessed domains compared to finerenone: reproductive (ROR 0.15, 95% CI 0.06-0.39), endocrine (ROR 0.20, 95% CI 0.07-0.58), psychiatric (ROR 0.26, 95% CI 0.16-0.43), and skin disorders (ROR 0.45, 95% CI 0.32-0.65). Hyperkalemia showed no directional signal (ROR 1.12, 95% CI 0.87-1.45). Notable individual spironolactone signals included polycystic ovaries, hypothyroidism, depression, and confusion.

Spironolactone generates substantially more spontaneous reports of hormonal, dermatological, and psychiatric adverse events in women than finerenone. While indication confounding and age differences limit direct causal inference, these reporting patterns align with finerenone's enhanced receptor selectivity. The persistent psychiatric signal for spironolactone warrants further investigation.